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Biomedical subjects

S Takagi

Publications and source records attributed to S Takagi.

At least 271 records · Page 15Linked to original sources

Identification of a highly specific surface marker of T-cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily.

Five monoclonal antibodies detected a surface antigen expressed exclusively on T-cell acute lymphoblastic leukemia (T-ALL) in a panel of 45 human hematopoietic cell lines, including T-cell lines derived from adult T-cell leukemia and those established by immortalization with human T-cell leukemia virus type 1 or Herpesvirus saimiri. Peripheral blood mononuclear cells, including fresh and activated T cells, were also completely devoid of this antigen. We designated this antigen as TALLA-1 (from T-ALL-associated antigen 1). By expression cloning, a cDNA clone encoding TALLA-1 was isolated from T-ALL cell line Molt-4. TALLA-1 was found to be a member of the transmembrane 4 superfamily (TM4SF). The cDNA was also essentially identical to A15, which was isolated from another T-ALL cell line, HPB-ALL, by differential hybridization with normal peripheral blood lymphocytes, and to CCG-B7, which was isolated from a brain cDNA library using CCG repeat as a probe. The gene product was now characterized in detail at the protein level. Northern blot analysis showed that the gene was expressed most strongly in brain, skeletal muscle and spleen. In a panel of 52 non-hematopoietic human cell lines, the majority of neuroblastoma cell lines were found to be positive for TALLA-1. Like ME491, CO-029 and L6, TALLA-1 may be another TM4SF member behaving as a potential tumor-associated antigen.

Amino Acid Sequence↗

Induction of ICAM-1 and LFA-3 by Tax1 of human T-cell leukemia virus type 1 and mechanism of down-regulation of ICAM-1 or LFA-1 in adult-T-cell-leukemia cell lines.

The present study was undertaken to determine the role of HTLV-I TaxI in the up-regulation of ICAM-I and LFA-3 in human T cells transformed with HTLV-I and the mechanism of down-regulation of ICAM-I and LFA-I in ATL-derived cell lines. Induction of TaxI in a human T-cell line Jurkat carrying the TaxI gene under the metallothionein promoter led to increases in mRNA and surface expression of ICAM-I. The response of LFA-3 to TaxI induction was, on the other hand, relatively slow and weak, and might be indirect. Transactivation of the ICAM-I promoter by TaxI was further shown by co-transfection of a CAT reporter construct with the ICAM-I promoter and a plasmid expressing TaxI. The mechanism of down-regulation of ICAM-I or LFA-I in 4 ATL cell lines was next examined. ICAM-I mRNA was quite low in MT-I, but no genomic changes were found. The CAT reporter with the ICAM-I promoter was inactive in MT-I. Finally, combined treatment of MT-I with 5-azacytidine and IFN-gamma induced re-expression of ICAM-I. Collectively, (a) transcriptional factor(s) necessary for expression of ICAM-I gene may be repressed in MT-I through DNA methylation. Three other ATL cell lines (TL-OmI, H582, HuT102) were found to have little mRNA for the LFA-I beta chain (CD18). H582 and HuT102 were also negative for the LFA-I alpha chain (CDIIa) mRNA. No genomic changes were found, and a CAT reporter gene with the CD18 promoter was inactive in the 3 of them, again suggesting lack of (a) transcriptional factor(s) necessary for CD18 expression.

Antigens, CD↗

Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system.

Neuropilin (previously known as the A5 protein) is a membrane protein identified in Xenopus and is presumed to be involved in the target recognition of the optic nerve fibers. We have isolated cDNAs encoding the chick homologue of neuropilin, using the Xenopus neuropilin cDNA as a hybridization probe. The predicted amino acid sequence of chick neuropilin is 75% identical to that of the Xenopus homologue. A cell aggregation assay showed that fibroblasts transfected with the chick neuropilin cDNA acquired cell adhesiveness. This adhesion is mediated by a heterophilic interaction between neuropilin and protease-sensitive molecules on fibroblasts. The expression of chick neuropilin is restricted to certain neuronal circuits and is dynamically regulated during development, as is the Xenopus homologue. However, their expression patterns differed significantly in the visual systems between the two species: In the chick optic tectum, the localization of neuropilin is confined to layers d and e of SGFS, two of the six layers receiving the retinal input; the chick optic nerve fibers do not express neuropilin; in the chick retina, amacrine cells transiently express neuropilin. Cultured neurons of the dorsal root ganglia express chick neuropilin on their neurites including growth cones. These results suggests that neuropilin functions as a cell adhesion molecule during the formation of certain neuronal circuits in vivo.

3T3 Cells↗

Splenectomy before tumor inoculation prolongs the survival time of cachectic mice.

The effects of splenectomy on the development of cachexia, tumor growth and animal survival were studied in tumor-bearing CDF1 mice. Mice were inoculated with two subclones of colon 26 adenocarcinoma, clone 20 (with a potent capacity to induce cachexia) and clone 5 (without such activity), and underwent splenectomy before or after tumor inoculation. Splenectomy significantly prolonged the survival of mice bearing clone 20 when it was performed prior to tumor inoculation, although the progression of cachexia and tumor growth were not affected. The survival rate was higher in splenectomized than it was in nonsplenectomized mice 20-40 days after tumor inoculation. Such effects on survival were not observed, however, in mice splenectomized after inoculation with clone 20 or in mice that underwent splenectomy either before or after inoculation with clone 5. The decrease of peripheral blood lymphocyte count observed in mice bearing clone 20 was magnified when splenectomy was performed before tumor inoculation, but the serum levels of tumor necrosis factor and interleukin-6 were comparable. These results indicate that cancer death from cachexia is not directly attributable to enhanced catabolism. The mechanism by which splenectomy ameliorates the survival of cachectic mice remains to be studied, although several changes observed in the splenectomized mice after inoculation, including decreases in the peripheral blood L3T4+ cells and Lyt-2+ cells on the 9th day and 15th day respectively, and increase in the L3T4+/Lyt-2+ cell ratio on the 15th day suggest the involvement of the modified host's immune response.

Adenocarcinoma↗

Convergence of laryngeal afferents with different natures upon cat NTS neurons.

To clarify the convergence of laryngeal afferents within the nucleus tractus solitarius (NTS) in the cat, we examined in the medulla the response characteristics of superior laryngeal nerve (SLN) fibers and NTS neurons to mechanical and chemical stimulation applied to laryngeal mucosa by extracellular recordings. The response was recorded in 75 SLN primary afferent fibers (PAFs) and 92 NTS neurons. PAFs of the SLN consisted of numerous monomodal mechanosensitive fibers and a small number of chemosensitive and polymodal fibers. On the other hand, the majority of NTS neurons had a polymodal nature. Thus, laryngeal information is considered to be integrated in modality into NTS neurons. All mechanosensitive fibers received information from a small restricted field in the larynx. On the contrary, each NTS neuron responded to mechanical stimulation over a wide laryngeal field, indicating that information from different sites spatially converge on NTS neurons. Our results suggest that caudal NTS neurons play a cardinal role in integrating laryngeal afferents, which are thought to elicit laryngeal reflexes.

Afferent Pathways↗

Plexin: a novel neuronal cell surface molecule that mediates cell adhesion via a homophilic binding mechanism in the presence of calcium ions.

Plexin (previously referred to as B2) is a neuronal cell surface molecule that has been identified in Xenopus. cDNA cloning reveals that plexin has no homology to known neuronal cell surface molecules but possesses, in its extracellular segment, three internal repeats of cysteine clusters that are homologous to the cysteine-rich domain of the c-met proto-oncogene protein product. The exogenous plexin proteins expressed on the surfaces of L cells by cDNA transfection mediate cell adhesion via a homophilic binding mechanism, under the presence of calcium ions. Plexin is expressed in the receptors and neurons of particular sensory systems. These findings indicate that plexin is a novel calcium-dependent cell adhesion molecule and suggest its involvement in specific neuronal cell interaction and/or contact.

Amino Acid Sequence↗

Pathology of equine respiratory disease occurring in association with transport.

Eight young thoroughbred horses, taken 1858 km by road (travelling time, 41 h), were examined to assess the pathological nature of respiratory disease associated with transport. Three of the horses showed clinical abnormalities including pyrexia, coughing, leucocytosis and neutrophilia after the first 20 h of transportation. Endoscopical examination of the trachea revealed exacerbation of airway inflammation as a result of transport in two of the three affected horses. A consistent finding in the affected horses was focal serous neutrophilic pneumonia affecting the cranio-ventral portion of the caudal lung lobe with a propensity to affect the right lung. Streptococcus equi subspecies zooepidemicus was isolated from the pneumonic areas, in which corresponding bacterial antigens were identified immunohistochemically. Viral cultures from the pneumonic lesions proved negative for respiratory viruses. It is suggested that transport predisposes the upper respiratory tract and the lower airways to invasion by the bacterium, with episodic pyrexia and acute pneumonia.

Acute Disease↗

Cyanamide-associated alcoholic liver disease: a sequential histological evaluation.

This is the first study that we are aware of that followed the histopathological progression of the liver disease that was caused by the combination of both chronic alcohol use and cyanamide, an antidipsotropic agent. Two sequential liver biopsy specimens were obtained on 29 alcoholics who relapsed with varying histories of cyanamide treatment. Cyanamide induced ground-glass inclusions (GGIs) in the hepatocytes. Two groups were identified, depending on whether GGIs proliferated or regressed, which was, in turn, found contingent on the duration of cyanamide treatment and the drug-free period. Group 1 included 14 cases in which GGIs either emerged only in the second biopsy specimen or else were increased in the second specimen as compared in the initial specimen. Group 2 composed of 15 cases in which GGIs were either not observed in either specimen or decreased in the second specimen as compared in the initial specimen. Acidophilic bodies were sequentially increased in five cases (36%) of group 1 and in none of group 2. The severity of portal inflammation worsened in 10 cases (71%) of group 1 but in 2 cases (13%) of group 2, although the changes in fibrotic process did not differ between two groups. These differences could not be explained on the basis of the daily ethanol consumption and the length of relapses of the two groups. Thus, when cyanamide-treated alcoholics relapsed, the combined effect of cyanamide and alcohol produced the development of acidophilic bodies and portal inflammation along with the emergence of GGIs.

Adult↗

Growth-associated expression of a membrane protein, neuropilin, in Xenopus optic nerve fibers.

Neuropilin (previously referred to as A5) is a neuronal cell surface protein which is widely distributed in such vertebrate species as Xenopus, chicken and mouse. In these vertebrate species, neuropilin is expressed in particular neuron circuits at particular developmental stages when axonal growth is active. To test whether the expression patterns of neuropilin is associated with axonal growth, we examined expression patterns of neuropilin in developing and regenerating Xenopus optic nerves. In embryos, a neuropilin-specific monoclonal antibody A5 (MAbA5) bound strongly to the optic nerves, and in situ hybridization signals for neuropilin mRNA were prominent in the retinal ganglion cells (RGCs), indicating that developing optic nerve fibers express neuropilin. The binding of MAbA5 to the optic nerve fibers was maximal at stages 41-43, then decreased in the subsequent tadpole life. In tadpoles after stage 50, the binding of MAbA5 to the optic nerves was extremely weak or almost nil, although RGCs expressed considerable amounts of neuropilin mRNA. When the tadpole optic nerves were crushed and prompted to regenerate, however, neuropilin protein reappeared in the optic nerve fibers. The binding of MAbA5 to the regenerating optic nerve fibers was detectable as early as the 5th day and maximal at the 2nd or 3rd weeks after the optic nerve crush, and declined thereafter. These findings suggest that the expression of neuropilin in the optic nerve fibers is regulated in an axonal growth-associated manner.

Animals↗

Alcohol and aldehyde dehydrogenase polymorphisms and the risk for alcoholism.

OBJECTIVE: The authors studied a large number of Japanese alcoholic patients and comparison subjects to establish the genotype frequencies of alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase (ALDH2) and to quantify the relative risk for alcoholism from the results. METHOD: The subjects were 655 alcoholic patients and 461 comparison subjects. ADH2 and ALDH2 were genotyped by the combination of polymerase chain reaction and hybridization methods. RESULTS: Active ALDH2 and usual ADH2 were significantly more frequent in the alcoholic patients. Inactive ALDH2 was not always associated with a low risk of alcoholism, and active ALDH2 was not always associated with high risk. In individuals with heterozygous inactive ALDH2 and usual ADH2, the odds ratio for alcoholism was high. CONCLUSIONS: The risk for alcoholism in Japanese has been accurately estimated on the basis of the genotype frequencies of ADH2 and ALDH2. Many Japanese may be protected from alcoholism by inactive ALDH2 and by higher frequencies of atypical ADH2.

Alcohol Dehydrogenase↗

Stationary organization of the actin cytoskeleton in Vallisneria: the role of stable microfilaments at the end walls.

In mesophyll cells of the aquatic angiosperm Vallisneria gigantea, bundles of microfilaments (MFs) serve as tracks for the rotational streaming of the cytoplasm, which occurs along the two longer side walls and the two shorter end walls. The stationary organization of these bundles has been shown to depend on the association of the bundles with the plasma membrane at the end walls. To identify the sites of such association, the effects of cytochalasin B (CB) on the configuration of the bundles of MFs were examined. In the case of the side walls, MFs were completely disrupted after treatment with CB at 100 micrograms/ml for 24 hours. By contrast, in the case of the end walls, a number of partially disrupted MFs remained even after 48 hours of treatment. After removal of CB, a completely normal arrangement of bundles of MFs was once again evident within 24 hours after a rather complicated process of reassembly. When reassembly had been completed, the direction of cytoplasmic streaming was reversed only in a small fraction of the treated cells, suggesting that bundles of MFs are anchored and stabilized at the end walls of each cell and that the polarity of reorganized bundles and, therefore, the direction of the cytoplasmic streaming is determined in a manner that depends on the original polarity of MFs that remained in spite of the disruptive action of CB. By contrast, the direction of reinitiated cytoplasmic streaming was reversed in 50% of cells in which the bundles of MFs had been completely disrupted by exogenously applied trypsin prior treatment with CB.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗

Effects of an HMG-CoA reductase inhibitor on cytokine production by human monocytes/macrophages.

It has been reported that the HMG-CoA reductase inhibitor simvastatin does not always effectively lower plasma LDL. This drug acts to monocytes/macrophages directly and inhibits cholesterol ester accumulation in these cells. However cytokine production in macrophages when simvastatin was administrated has not been described. In this study, we examined whether simvastatin affects cytokine production in human monocyte-derived macrophages. Simvastatin at doses ranging from 10(-9) to 10(-5) M did not affect the synthesis of proinflammatory cytokines (IL-1 beta, IL-6, IL-8) from human peripheral mononuclear cells. In addition, any changes in cytokine-induced cytokine production (IL-1-induced IL-8 synthesis) were not detected after the addition of simvastatin. The present results suggest that simvastatin suppresses foam cell formation in monocyte/macrophage, without affecting the immunological or inflammatory functions of these cells.

Cells, Cultured↗

Collaborative work to determine an optimal administration period and optimal parameters for detection of effects on male fertility in rats--male reproductive toxicity study of haloperidol.

Haloperidol, a neuroleptic, was orally administered at 0, 3, 10, 30 and 60 mg/kg/day in a 4-week dosing study, and 0, 3, 10 and 30 mg/kg/day in a 9-week dosing study, to Sprague-Dawley male rats which were then sacrificed for histopathological examination or mated with untreated females. The males in the mating groups were continuously treated during the mating period. Sperm positive females were sacrificed on day 20 of gestation. The males in the histopathology groups were sacrificed after 4- or 9-week dosing and their testes were fixed in Bouin's fluid and sections stained with HE or PAS. The mated males were sacrificed and reproductive organ weights were determined. At 3 mg/kg or more, reduced spontaneous motor activity was observed and body weights were lowered. The absolute weight of testes was decreased with 60 mg/kg in the 4-week dosing study, and was decreased with 10 and 30 mg/kg in the 9-week dosing study. However, the relative weight was increased or showed a tendency to increase. In the 4-week dosing study, decrease in the fertility index with 60 mg/kg and increase in pre-implantation loss with 30 mg/kg or more were noted. However, there were no adverse effects on the copulation index in any of the treated groups. The males given 60 mg/kg showed slight changes in the testes (necrosis of pachytene spermatocytes in seminiferous tubules of stage VII, exfoliation of round spermatids in the lumina and atrophy of Leydig cells) and seminal vesicles (atrophy of epithelial cells). Atrophy of Leydig cells was also observed at 30 mg/kg in the 4-week dosing study. In the 9-week dosing study, neither male reproductive ability nor histopathological parameters were affected by haloperidol up to 30 mg/kg. From the results detailed above, it may be concluded that 4-weeks dosing before mating is suitable for detection of effects of haloperidol on male reproductive ability, and that histopathological changes together provide an optimal parameter for predicting male reproductive disorders.

Animals↗

[Effect of oak pollen on patients with birch pollinosis].

The author reviewed 53 cases of birch pollinosis treated in our ENT-clinic between 1990 and 1991. Of interest is the fact that many of these patients complained of typical symptoms in and after June, when birch pollen has usually disappeared. We considered this discrepancy to be attributable to the effects of grass pollen, one of the common causal agents in this period. However, only a few patients tested positive for grass pollinosis. We therefore postulated that cross-reactivity between birch and oak pollen accounted for this phenomenon, because both trees belong to same order, Fagales. A strong correlation between RAST scores for birch and oak pollen was detected, and the oak pollen RAST score was significantly reduced by birch pollen extract in an inhibition test. These findings demonstrated actual cross-reactivity between birch and oak pollen. Birch pollinosis patients in Sapporo therefore have allergic symptoms from March to July.

Cross Reactions↗

Remineralization of root lesions with concentrated calcium and phosphate solutions.

Remineralization of enamel lesions in vitro by use of sequential treatments with an alkaline (pH 9) phosphate (1 mol/L) solution and slightly acidic (pH 6) calcium (1 mol/L) solution was reported to be relatively ineffective. An analysis of the diffusion processes that may occur during the remineralization treatments suggested that the driving force for diffusion of Ca into the lesion can be increased by making the calcium solution more alkaline than the phosphate solution. In the present study this modified treatment procedure was evaluated for remineralizing root lesions in vitro. Results show that (1) in the control group there was a slight increase in mineral density in the surface region of the lesion, (2) in the experimental group there were significant (p < 0.05) increase in mineral content in the outer 40 microns of the lesion, and (3) in contrast to the finding reported previously, thick mineral deposits on the surface of the root were not observed.

Calcium↗

Histopathological reaction of calcium phosphate cement in periodontal bone defect.

In this study, we evaluated the osteoconductivity of calcium phosphate cement (CPC) as compared to that of a current hydroxyapatite-based material (AP) by implanting the materials in surgically formed defects in the jaws of dogs. One month post-operation, slight inflammatory reactions were observed in tissue areas adjacent to either CPC mass or AP. Three months after operation, the CPC mass-filled defects were covered with periosteum and bone tissues. The CPC mass in the defects was partially replaced by newly formed bone. In bone defects filled with AP, most of the interparticle space was filled with connective tissues including bone tissues. Six months post-operation, the CPC mass-filled defects were covered with periosteum and new bone, and most of the CPC mass was replaced by bone. Interparticle spaces of AP were filled with connective tissues and bone tissues.

Alveolar Bone Loss↗