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Biomedical subjects

H Honda

Publications and source records attributed to H Honda.

At least 253 records · Page 14Linked to original sources

Antibodies against leukocyte function-associated antigen-1 and against intercellular adhesion molecule-1 together suppress the progression of experimental allergic encephalomyelitis.

We obtained the evidence that coadministration in vivo of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) suppressed the progression of experimental allergic encephalomyelitis (EAE) in rats. The suppressive effect in vivo of coadministration of the mAbs during the induction phase was not prominent, but the administration of these mAbs during the effector phase markedly suppressed the progression of clinical illness and prevented the infiltration of encephalitogenic cells into the central nervous system. However, administration of the mAb to LFA-1 alone or ICAM-1 alone did not show such suppressive effects. These findings suggest that LFA-1 and ICAM-1 are critically involved in the development of EAE and that the administration together of mAbs against adhesion molecules including LFA-1 and ICAM-1 might provide a new immunotherapeutic approach for the treatment of multiple sclerosis.

Animals↗

Murine monoclonal antibody recognizing human alpha(1,3/1,4)fucosyltransferase.

We prepared a mouse monoclonal antibody, FTA1-16, that specifically recognizes human alpha(1,3/1,4)fucosyltransferase without crossreactivity to any other members of the alpha(1,3)fucosyltransferase family. The specificity was confirmed by both immunofluorescense staining of native antigens in the Golgi apparatus and Western blotting analysis, using stable transformant cells transfected with each gene of the alpha(1,3)fucosyltransferase family. Western blotting analysis on a series of human tumour cell lines from various tissues revealed that some epithelial cancer cell lines from digestive organs expressed an amount of alpha(1,3/1,4)fucosyltransferase in good correlation with expression of sialyl Lewis a antigen. Immunohistochemical staining by FTA1-16 on colon cancer tissues revealed enhanced expression of the enzyme in cancer cells in comparison to normal cells. Finally, the antigenic epitope recognized by FTA1-16 was determined using truncated recombinant peptides which were expressed in E. coli. A minimal length determined was a fragment, amino acid positions 132-153, of the alpha(1,3/1,4)fucosyltransferase.

Amino Acid Sequence↗

Adsorption of monomers on microspherical structures of thermal heterocomplex molecules from amino acids.

The surface of a microspherical structure formed in the aqueous suspension of thermal heterocomplex molecules made by heating aspartic acid and proline can adsorb basic amino acids such as histidine, lysine and arginine. It can also adsorb adenine, cytosine, adenosine and cytidine. Electrostatic interactions acting between those monomers to be adsorbed and the absorbing surface are responsible for the adsorption.

Adenine↗

Auranofin inhibits calcium uptake into opsonized-zymosan-stimulated neutrophils obtained from rats.

In order to study the pharmacological action site of auranofin during the functional suppression of leukocytes, especially neutrophils, we investigated the influence of auranofin on the calcium-45 (45Ca2+) uptake into peripheral blood neutrophils and peritoneal resident macrophages isolated from normal and adjuvant-induced arthritis (AA) rats. Calcium-45 uptake into neutrophils and macrophages obtained from normal and AA rats was increased by stimulation with opsonized-zymosan, while auranofin inhibited the increase in the 45Ca2+ uptake into neutrophils, but not into macrophages. There was a tendency that auranofin more strongly inhibited the increase in the 45Ca2+ uptake into neutrophils obtained from AA rats than normal rats, but no statistically significant difference between them was observed in the inhibitory potency of auranofin. From these results, it is suggested that auranofin would show anti-rheumatic and anti-inflammatory effects by the inhibition of Ca2+ uptake into neutrophils which infiltrate into local lesions during the early and active phases of rheumatoid arthritis.

Animals↗

Visual mislocalization produced by a rapid image displacement on the retina: examination by means of dichoptic presentation of a target and its background scene.

The time course of visual mislocalization produced by a rapid retinal image displacement was examined in moving-background and saccadic eye movement experiments. In both experiments, the target for localization task and its background scene were dichoptically presented: they were presented separately to the different eyes. The error curves of mislocalization shown in the dichoptic viewing condition were the same as those in monocular viewing (in the moving-background experiment) and binocular viewing conditions (in the saccadic eye movement experiment), indicating that in both experiments the neural interaction responsible for generating mislocalization took place at a site after the lateral geniculate nucleus in the visual system, not at the retinal level. Two possible explanations for mislocalization, one neurophysiological and the other cognitive, were proposed. Furthermore, it was established that the error curves of mislocalization are substantially different between the moving-background and the saccadic eye movement experiments: in the saccadic eye movement experiment, the error curves changed with the actual target position, but not in the moving-background experiment. This was interpreted as showing that the basic mechanism for mislocalization is not the same between the two experimental situations.

Fixation, Ocular↗

Slow and macroscopic modulation of thermal fluctuations in myofibrils.

A comparison was made between fluctuations in a length of sarcomere from a myofibril during relaxed and rigor conditions. The fluctuations of the length associated with rigor states was due entirely to thermal fluctuations in the ambient. In contrast, the fluctuations associated with relaxed states were accompanied by extremely slow and macroscopically modulated thermal fluctuations. A slow, macroscopic modulation of the thermal fluctuations of the length of sarcomere was found to be unique to myofibrils in their relaxed conditions.

Animals↗

ATP hydrolysis and sliding movement of actomyosin complex in the presence of ethanol.

We measured both the ATPase activity of actomyosin complex and the sliding velocity of actin filaments on myosin heads under hydrophobic conditions in the presence of ethanol. Both the ATPase activity and the sliding velocity decrease with the increase of ethanol concentration, if the ionic strength is not too high. As ionic strength increases, there appears an optimum concentration of ethanol that can enhance both the ATPase activity and the sliding velocity.

Actomyosin↗

Small hepatocellular carcinomas undetected on two-phased incremental computed tomography. Angiographic and clinicopathologic findings.

RATIONALE AND OBJECTIVES: To elucidate the characteristic clinicopathologic features of hepatocellular carcinomas (HCCs) undetected on two-phased incremental computed tomography (CT). METHODS: Computed tomographic scans of 115 surgically resected small (< or = 3 cm) HCCs from 83 patients were performed 45 seconds and 6 minutes after the administration of contrast material. These scans were compared with corresponding angiographic and histopathologic findings. RESULTS: Eighty HCCs (70%) were depicted on the early images; 73 (63%) on the delayed images; and 89 (77%) using two-phased incremental CT. The small HCCs undetected on the early images but seen histologically had the following characteristics: (1) absence of a fibrous capsule, (2) well-differentiated tumor, (3) replacing growth patterns of the tumors, (4) lack of fatty metamorphosis and/or clear cell changes, (5) hypovascular on angiography. Those not seen on delayed images had the following characteristics: (1) absence of a fibrous capsule, (2) replacing growth patterns, and (3) presence of portal tracts in the tumors. CONCLUSIONS: The replacing growth pattern and the presence of portal tracts correlate with the undetectability on CT. For HCCs undetected on CT, treatment methods must be considered carefully, because the HCCs may be receiving transsinusoidal and portal blood supplies.

Adult↗

Of the GATA-binding proteins, only GATA-4 selectively regulates the human interleukin-5 gene promoter in interleukin-5-producing cells which express multiple GATA-binding proteins.

Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B-cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region within the human IL-5 gene promoter that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of this family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and phorbol-12-myristate-13-acetate (PMA)-A23187 stimulation are necessary for IL-5 promoter activation. The requirement for another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNAs of three GATA-binding proteins, hGATA-2, hGATA-3, and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms a specific DNA-protein complex with the -70 GATA site. An electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity for the -70 GATA site among the three GATA-binding proteins. When the transactivation abilities were compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed.

Amino Acid Sequence↗

Lymph-node metastases: efficacy for detection with helical CT in patients with gastric cancer.

PURPOSE: To determine the efficacy of helical computed tomography (CT) in the detection of lymphadenopathy in patients with gastric cancer. MATERIALS AND METHODS: Helical CT (5-mm section thickness, 5-mm/sec table incrementation) was performed in 58 patients (39 men, 19 women; mean age, 63.8 years) with gastric cancer; 1,082 lymph nodes (138 positive, 944 negative for metastasis) were resected at surgery. Findings at CT and resection were compared. Sensitivity for detecting lymph nodes was evaluated according to nodal size and presence of metastasis. RESULTS: Seven (1.1%) of 649 lymph nodes 1-4 mm, 160 (45.1%) of 355 nodes 5-9 mm, and 56 (72%) of 78 nodes larger than 9 mm were detected at CT. For nodes of at least 5 mm, sensitivity for detecting metastasis-positive nodes (79 [75.2%] of 105 nodes) was higher than that for detecting metastasis-negative nodes (137 [41.8%] of 328; P < .01). Differences between positive and negative nodes in CT attenuation (110 HU +/- 25 vs 66 HU +/- 32) and short-to-long axis ratios (0.81 +/- 0.15 vs 0.57 +/- 0.15; P < .001) were significant. CONCLUSION: Helical CT is effective for detection of metastatic lymphadenopathy from gastric cancer. CT attenuation and lymph-node configuration aid in diagnosis of malignant adenopathy.

Adult↗

Xanthine derivatives inhibit the increase in intracellular Ca2+ concentration induced by acetylcholine in nasal gland acinar cells of the guinea-pig.

Intracellular calcium is considered to play a major role in secretory responses of various exocrine cell types. We examined whether xanthine derivatives can inhibit Ca2+ mobilization and entry in secretory cells in the airways. Therefore, the inhibitory effect of xanthines in the intracellular Ca2+ concentration ([Ca2+]i) in the isolated submucosal acinar cells of the guinea-pig nasal septum was investigated by means of fluorescence ratio microscopy. The inhibitory effects on Ca2+ release from stores was examined in Ca(2+)-free conditions. Effects on Ca2+ entry were estimated by two different protocols; 1) the sustained phase in a long-term application of acetylcholine (ACh) and 2) the [Ca2+]i overshoot following removal of ACh in Ca(2+)-free conditions. Xanthine derivatives, 3-isobutyl-1-methyl-xanthine (IBMX), caffeine, and theophylline, significantly inhibited the increase in [Ca2+]i evoked by ACh; both mobilization from internal Ca2+ stores and Ca2+ entry from the external space. The rank order of potency of these xanthine derivatives was IBMX > theophylline > caffeine. The addition of dibutyryl-cyclic adenosine monophosphate (cAMP) and forskolin to nasal gland acinar cells failed to inhibit the ACh-evoked increase in [Ca2+]i. Furthermore, a protein kinase A inhibitor, H-89, did not affect the inhibitory effect of the xanthine derivatives. The action of xanthines on the present acinar cells did not involve Ca(2+)-induced Ca2+ release (CICR) or an interaction with purinergic receptors. Thus, xanthines have a direct inhibitory effect both on Ca2+ release and entry in nasal gland acinar cells, and might thereby have antisecretory activity within the airways.

Acetylcholine↗

Transmission of dystrophinopathy by X-chromosome inversion.

A woman had a karyotype of 46Xinv(X)(p21.2;q26.1) and mosaicism of dystrophin-negative muscle fibers. The X-chromosome inversion was transmitted to her daughter, who had an elevated serum CK. The genetic transmission as well as the probable random inactivation of the abnormal X chromosome in this mildly affected patient distinguish this case from those of dystrophinopathy with X;autosome translocations.

Chromosome Inversion↗

The changes of maternal deaths in Japan.

Maternal deaths in Japan are compared and discussed with those of highly developed countries. It is still higher in this country than in other highly developed ones, and we think it is necessary to furnish the tertially emergency hospitals and maternal transfer system.

Ambulatory Care Facilities↗

Increased regional systolic myocardial stiffness of the left ventricle during coronary artery occlusion in a dog: analysis of the finite element model.

(1) We measured the instantaneous systolic transfer function of an isolated canine left ventricle (LV) before and after the ligation of the left anterior descending coronary artery (LAD). The instantaneous transfer function before the ligation of the LAD showed a resonance curve whose peak frequency was 30 to 70 Hz. On the other hand, the transfer function 40 min after the ligation of the LAD showed a divided peak in the resonance curve. (2) We constructed a finite element model of a thick-walled spherical shell with a non-uniform structure. In this model, the myocardial elasticity and viscosity of the ischemic region are different from those of non-ischemic regions. One can calculate the theoretical transfer function using modal analysis and also estimate the elasticity and the viscous coefficient of both non-ischemic and ischemic myocardium by fitting the theoretical transfer function to the experimental one. (3) The estimated elasticity of the ischemic myocardium was three to five times larger than that of the non-ischemic myocardium. The estimated viscous coefficient of the ischemic myocardium was about half that of the non-ischemic myocardium. These results showed that ischemia alters the viscoelastic properties of the myocardium during systole as well as during diastole.

Animals↗

[Intra-bile duct growth of hepatocellular carcinoma: value of biliary dilatation on CT].

In order to evaluate the usefulness of CT in demonstrating biliary invasion by hepatocellular carcinoma, 191 surgically proved cases were studied. Among 191 CT scans performed before surgery, six (3%) showed biliary dilatation. Pathological biliary invasion was found in eight cases (4%). Of these eight cases, four cases (50%) showed biliary dilatation on CT. In six cases with biliary dilatation on CT, pathological biliary invasion was revealed in four cases (67%). In two cases, the large (> or = 6cm) encapsulated tumors located in the hepatic hilum dilated the intrahepatic bile duct without intraductal tumor growth. We concluded that biliary dilatation on CT cannot be a sign of biliary invasion by hepatocellular carcinoma.

Adult↗

[An animal model of leukemogenesis using transgenic mice].

The bcr/abl chimeric oncoprotein is considered to be implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. To investigate its biological function and the role in leukemogenesis in vivo, we generated transgenic mice expressing p210bcr/abl driven by the metallothionein promoter. Two of six founder mice and the transgenic progeny of one leukemic founder mouse developed leukemias several months after birth. Phenotypically, each leukemic mouse showed a thymic enlargement, a marked splenomegaly, and/or lymphnode swellings. Pathological examination revealed that leukemic cells were infiltrated in all tissues examined, especially in thymus, spleen, liver, and lymphnode. Expression of the p210bcr/abl transgene product and increased phosphorylation of cellular proteins in leukemic tissues were detected by the Western blot analysis. In addition, the expressed p210bcr/abl protein was demonstrated to possess an enhanced kinase activity by the in vitro immunecomplex kinase assay. These results indicate that hematopoietic precursor cells expressing the p210bcr/abl transgene product acquired a proliferative advantage and eventually developed leukemias in transgenic mice. The p210bcr/abl transgenic mice are considered to be an excellent animal model to investigate p210bcr/abl function and its role in leukemogenesis in vivo.

Animals↗

[Immunohistochemical studies on pathogenetic features of diffuse fasciitis].

Three cases of diffuse fasciitis were reported: case 1, a 24-year-old female, case 2, an 18-year-old male and case 3, a 61-year-old male. Their prominent features were reduced extensibility of the muscle and/or fascia. Skin was taut and bound underneath in cases 1 and 3, and focal edema was noted in the left forearm of case 2. Firmness of the muscle and/or fascia was dominantly seen in four extremities in case 1, proximal limbs in case 2 and in the trunk and proximal limbs in case 3. Muscle weakness was not seen in case 1, slight in the limbs of case 2 and moderate in the proximal limbs of case 3. Transient eosinophilia was observed in case 1. IgG was elevated in all 3 cases and IgM in cases 1 and 3. Antinuclear antibody was positive in case 1 and 2, and anti-ENA antibody in case 3. Remarkable thickening of the fascia and perivascular mononuclear cell infiltration in the fascia were main pathological features in all three cases. Inflammatory alteration of the muscle was modest and limited to the perifascicular and epimysial sites underneath the fascia. In these 3 cases, a diagnosis of Shulman syndrome or diffuse fasciitis with eosinophilia was made, although eosinophils were scarce in the fascia or muscle tissue. All 3 cases well responded to the oral prednisolone. Mononuclear cells clustered mainly in the perivascular sites, comprising mostly T cells, helper T cells, and partly B cells. These findings suggest that helper T cell mediated immune mechanism may play a pathogenetic role in this disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗