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Biomedical subjects

S Miyatake

Publications and source records attributed to S Miyatake.

At least 91 records · Page 5Linked to original sources

Treatment of a giant aneurysm of the cavernous internal carotid artery associated with a persistent primitive trigeminal artery: case report.

A case of an unruptured giant aneurysm of the cavernous portion of the left internal carotid artery associated with a persistent primitive trigeminal artery (PTA) is presented. The usual surgical approach to giant aneurysms at this site, including ligation of the ipsilateral internal carotid artery (ICA) and an extracranial-intracranial (EC-IC) bypass, was inadequate because of continued blood supply to the aneurysm via the PTA from the vertebrobasilar system. The patient was successfully treated with a combination of EC-IC bypass surgery, ICA ligation, and simultaneous intravascular balloon obliteration of the ICA just distal to the junction of the PTA and immediately proximal to the aneurysmal neck. Follow-up radiological investigations showed thrombosis of the aneurysm.

Carotid Artery, Internal↗

[Basic studies on glass ceramics. 3. Influence on calcification of osteogenic cells in vitro].

Two established osteogenic cell lines (NY, MC 3 T3-E 1) were used in vitro to determine the biocompatibility of glass ceramics and their effect on initial calcification of osteogenic cells. Morphological study of the cell under the phase-contrast microscopy and histochemical staining were applied as follows. First, glass ceramic granules were placed in 60 mm dishes, and cells were suspended in the dishes in alpha-MEM supplemented with 10% FBS (basic medium) or medium with 50 micrograms/ml of L-ascorbic acid added. After 8 or 14 day of culturing, calcium formation was tested by von-Kossa's staining. Also, alkaline phosphatase staining was performed by the azo-dye method. As controls, cultures in dishes without glass ceramic granules were stained at the same time. The results obtained in the experimental culture were as follows. 1. Phase contrast microscopy showed that contacts with glass ceramics did not cause cellular death or degeneration. 2. In both cell cultures with the glass ceramics the von-Kossa reaction was positive as early as the 8th day. 3. The alkaline phosphatase reaction on the 8th day occurred only in MC 3 T3-E 1. The reaction was localized on fibroblastic cells which proliferated three-dimensionally around glass ceramics, and on small polyhedral cells situated relatively for apart from the ceramics. 4. On the 14th day, the MC 3 T 3-E 1 formed large nodules around the glass ceramics, and they were stained uniformly positive by von-Kossa's method. The alkaline phosphatase-positive cells extended spoke-like forms. 5. In medium with L-ascorbic acid, growth of NY was inhibited, After being cultured for 14 days, abundant von-Kossa positive reaction was found around glass ceramics in both cells. In MC 3 T 3-E1 on the 8th days, the alkaline phosphatase reaction was stronger with glass ceramics than with basic medium only. On the contrary, in the control cultures of both cells there was negative von-Kossa reaction during the culture period. The above results showed that glass ceramic granules have the biocompatibility needed for bone grafts, and they facilitated calcification of MC 3 T 3-E 1 in culture.

Alkaline Phosphatase↗

Interleukin 5 enhances interleukin 2-mediated lymphokine-activated killer activity.

IL-5 expresses various biologic effects on several types of lymphocytes, including B cells, eosinophils, and T cells. We demonstrated that the incubation of resting splenocytes from C57BL/6 mice in murine rIL-5 enhances IL-2-mediated lymphokine-activated killer (LAK) activity against various tumor cells. IL-5 alone, however, does not induce killer activity. IL-2-mediated LAK activity increases in proportion to the dose of IL-5. During the late phase of the culture period, IL-5 seems to have some effect on the induction of IL-2-mediated LAK activity. We expect that IL-5 will prove useful for adoptive immunotherapy.

Animals↗

Bovine papilloma virus encoded E2 protein activates lymphokine genes through DNA elements, distinct from the consensus motif, in the long control region of its own genome.

Activation of T cells by antigen, lectin or a combination of phorbol ester (PMA) and calcium ionophore (A23187) leads to the induction of a set of lymphokine genes. Transfection of a human T cell leukemia cell line, Jurkat, or an African green monkey kidney cell line, CV1, with a cDNA encoding E2 protein, a trans-activator of bovine papilloma virus type 1, results in activation of interleukin 2 (IL-2), interleukin 3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) genes in a transient transfection assay. 5' deletion and mutation analyses showed that the sequence between positions -60 and a TATA-like sequence is required for basic promotor function and that the sequence between positions -95 and -73 containing conserved lymphokine element 2 (CLE2) and a GC box (CLE2/GC box) mediates the positive response to E2 protein. The latter has been previously shown to respond to PMA/A23187 stimulation or to p40tax, a trans-activator encoded by human T cell leukemia virus type 1 (HTLV-I). The sequence located between -108 and -99 (CLE1) is inhibitory to E2 protein or PMA/A23187 stimulation. The combination of E2 protein and PMA/A23187 appears to eliminate an inhibitory effect of the upstream region. However, E2 protein, like p40tax, mediates a positive response through CLE1 alone linked to the basic promoter sequence. The level of activation of the long control region (LCR) by E2 protein is unaffected by the number of CLE2/GC box sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Expression of proto-oncogene products during drug-induced differentiation of a neuroblastoma cell line SK-N-DZ.

Four human neuroblastoma cell lines exhibited differences in their ability to differentiate into neuron-like cells in response to three different treatments, serum deprivation, or additions of dibutyryl cyclic-AMP or retinoic acid. Expression of N-myc gene product was reduced in neuroblastoma cell line SK-N-DZ differentiated by retinoic acid as compared with untreated cells. On the contrary, expression of c-src gene product, pp60c-src, was considerably enhanced in differentiated SK-N-DZ cells. Tyrosine phosphorylation of several cellular proteins was found to be enhanced in differentiated cells. Alteration in expression of these proto-oncogene products might be important in the differentiation of neuroblastoma cells into neuron-like cells.

Bucladesine↗

Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity.

To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the major histocompatibility complex class I antigens at the cell surface and the transcription levels, irrespective of their IFN-gamma-producing potential. Although in vitro cell growth of these cells was unaffected by the IFN-gamma production, their s.c. tumor growth in syngeneic A/J mice was dependent upon levels of IFN-gamma production; tumors induced by a low-producer line grew well at a rate similar to those induced by the parental one, but tumor growth of a high-producer line was strongly suppressed. This apparent tumor suppression was abolished by simultaneous i.p. injection of anti-Lyt2.2 and/or anti-IFN-gamma monoclonal antibodies, and subsequently large tumors of the high producer were generated. Anti-asialoganglioside GM1 antibodies allowed the high-producer line to induce a substantial but only transient tumor growth, whereas other antibodies, such as anti-Lyt2.1, anti-IFN-beta, and anti-activated macrophage, had no such effect. The mice immunized with the high-producer line were resistant to tumor growth of the parental cells but permitted another kind of A/J tumor line, Sa-1, to induce remarkable tumors. These results indicate that the reduced tumorigenicity of the IFN-gamma high-producer line was due to the augmented specific anti-tumor immunity, in which cytotoxic T lymphocytes seemed to play a decisive role, probably as a result of the immunomodulatory effects of the IFN-gamma derived from the tumor.

Animals↗

[Application of calcium phosphate ceramics to periodontal therapy. 8. Effects of orthodontic force on repaired bone with hydroxyapatite].

It has been unclear whether M.T.M. is acceptable for patients treated with bone grafts using hydroxyapatite (HAP), which is not biodegradable. Therefore we studied histological changes in bone among HAP during orthodontic tooth movement. HAP was implanted into artificial bone defects adjacent to second premolars in beagle dogs, and as a control no material was implanted Three months after implantation, the second premolars were moved with orthodontic force. Then they were observed histopathologically. The results obtained were as follows. The amount of movement of the teeth in implanted sites was less than in the controls. In the pressure zone, resorption of bone by osteoclasts was observed in both the implanted and the control sites, in addition, root resorption occurred adjacent to HAP. Furthermore multinucleated giant cells were closely attached to HAP and were surrounded by bone and connective tissue. In retention period there was ankylosis between the roots and bone around HAP. In the tension zone, additional bone from HAP was observed. Bone defects were filled with bone in the implanted sites, but with connective tissue in the controls. These results suggest that bone among HAP was resolved by osteoclasts. Clinically, HAP implantation for the pressure zone should be avoided because of the occurrence of root resorption and ankylosis. But for the tension zone it seems to be effective because HAP implantation produces more repaired bone.

Animals↗

[Hydroxyapatite implant for human periodontal osseous defects].

The purpose of this study was to evaluate the efficacy of porous hydroxyapatite (HAP) as an implant material into human periodontal defects. Thirty three patients affected by marginal periodontitis were studied. Following initial therapy, 44 periodontal osseous defects received grafts of HAP granules and blocks during flap surgery. Radiographic and various clinical examinations were performed before surgery and 1 and 2 weeks, and 1, 2, 3, 6 and more than 6 months after surgery. The results were as follows: 1. Postsurgical inflammation of the gingiva disappeared in a short time. Further more open wounds and discharges of HAP disappeared in the first month. There were no clinical problems in the sites receiving HAP implantation. 2. Radiographic demarcation lines between the implanted HAP and the surrounding alveolar bone became unclear at the beginning of bone repair. 3. At six months after surgery, the mean values of gingival recession, decrease in pocket depth and clinical attachment gain were respectively 0.9 mm, 2.7 mm, 1.9 mm. Additional observation beyond 6 months showed an attachment gain of 2.0 mm. 4. The attachment gain was less in the cases of one wall osseous defect and of furcation involvement in lower molars. These results suggest that HAP implantation is clinically effective, however, careful application is needed for the cases of one wall osseous defect or furcation involvement.

Dental Implants↗

Murine intracerebral interleukin-2 injection: pathological and immunological effects.

The authors have investigated whether specific pathological changes and antibodies against interleukin-2 (IL-2) are induced after intracerebral administration of recombinant IL-2 (rIL-2). In addition, IL-2 receptor (IL-2R) expression was checked on the cell surface of normal brain tissues before and after the intracerebral infusion. Reconstituted rIL-2 (specific activity 1.2 x 10(7) U/mg protein) was injected into the right cerebral hemisphere of normal adult C57BL/6 mice in three different dose groups, each receiving single or multiple infusions of 8, 32, or 80 U. In sham control experiments, mouse albumin purified by gel filtration and ion exchange chromatography and adjusted to the same concentration of protein as rIL-2 was injected into mice at various doses. Anti-IL-2 antibodies were measured by an enzyme-linked immunosorbent assay concurrently with assessment of IL-2 activity in serum. The IL-2R expression was determined by using immunofluorescence techniques with monoclonal antibodies against mouse IL-2R. Since histological alteration after rIL-2 injection did not differ from that in the sham control preparations, it seems that there is no direct toxic action of rIL-2 on normal brain tissues. Interleukin-2 antibodies were produced at low levels only in mice injected repeatedly at the maximum dose, and levels were insignificant in other groups. Serum levels of IL-2 activity remained low. The IL-2R expression within the brain was not enhanced within 8 weeks following the intracerebral administration of rIL-2, suggesting that direct intracerebral infusion of rIL-2 may be safely used in the immunotherapy of brain tumors.

Animals↗

Augmentation of tumor targeting in a line of glioma-specific mouse cytotoxic T-lymphocytes by retroviral expression of mouse gamma-interferon complementary DNA.

As an initial approach to experiments directed toward effective adoptive immunotherapy for cancer using lymphokine genes, we transferred retrovirally a complementary DNA encoding mouse gamma-interferon (IFN-gamma) into a specific cytotoxic T-lymphocyte clone, designated E-4, against 203 glioma cells (a 20-methylcholanthrene-induced mouse glioma line) and confirmed the efficacy of IFN-gamma production from the exogenous gene on augmentation of tumor targeting. Of five, two gene-transferred subclones constitutively produced 8 to 10 times the amount of IFN-gamma as compared with the parental E-4. Correspondingly, these two subclones exhibited 2 to 3 times higher killing activity against 203 glioma than the parental cells; the enhancement of the killing activities was abrogated by an adequate addition of anti-IFN-gamma antibody. No alteration was seen after the gene transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+,3+, and asialo-GM1-. The surface expression of a major histocompatibility complex Class I antigen, H-2Kb, was not altered remarkably, but the Class II antigen, I-Ab, was partially and slightly enhanced on the two IFN-gamma-producing sublines mentioned above on fluorescence-activated cell sorter analysis. Since it is considered that in the vicinity of the constitutively IFN-gamma producing cytotoxic T-lymphocyte cells tumor cells are exposed to a high concentration of IFN-gamma, the cells may be stimulated to induce or enhance the expression of surface antigens including major histocompatibility complex antigens as well as tumor-associated antigens relevant to immune recognition. The 203 glioma cells pretreated with IFN-gamma were more efficiently killed by both the parental E-4 and the gene-transferred sublines. Taken together, the results suggested that the augmented specific tumor-killing activity of our gene-transferred cytotoxic T-lymphocytes was ascribed to the constitutive production of IFN-gamma derived from the exogenous gene.

Animals↗

Activation of T cell-derived lymphokine genes in T cells and fibroblasts: effects of human T cell leukemia virus type I p40x protein and bovine papilloma virus encoded E2 protein.

The effects of p40x, a product of an human T cell leukemia virus type I, on the activation of lymphokine genes were examined. The mouse GM-CSF and IL-3 genes were activated by cotransfection with a pX containing plasmid both in Jurkat and CV1 cells. Mouse GM-CSF gene was also activated by phytohaemagglutinin A (PHA)/phorbol myristate acetate (PMA) or PMA/calcium ionophore A23187 stimulation. The 5'-flanking region of the mouse GM-CSF gene which is required for activation by pX or mitogen was mapped within 226 bp upstream from the transcription initiation site. Action of pX was not restricted to T cells. pX activated exogenously added GM-CSF, IL-2, IL-3 and IL-4 genes in fibroblasts. Activation of the GM-CSF gene in fibroblasts appears to require the same regulatory region as in T cells. Similar results were obtained using bovine papilloma virus encoded E2 protein. We propose that pX or E2 protein, both in T cells and fibroblasts, activates cellular component(s) in the signal transduction pathway which results in the activation of lymphokine genes in the absence of extracellular stimuli.

Adenovirus Early Proteins↗

Coordinate regulation of immune and inflammatory responses by T cell-derived lymphokines.

In response to antigenic stimulation, helper T cells secrete a set of protein mediators called lymphokines that regulate proliferation, differentiation, and maturation of lymphocytes and hemopoietic cells. Because all known lymphokines are composed of a single polypeptide chain, their coding sequences can be isolated by functional expression in appropriate host cells. Based on this expression cloning protocol, a number of T cell lymphokine genes have been isolated, their primary structure has been determined, and biological properties of their recombinant products have been examined. These studies revealed the existence of a regulatory network between lymphoid cells and hemopoietic cells mediated by the actions of multiple pleiotropic lymphokines produced by activated T cells. Because all or a part of this network can be activated in different ways by unique combinations of lymphokines, it is clear that T cells can play a vital role in coordinating the function of different body compartments in the immune and inflammatory responses. The activation of lymphokine genes in T cells by antigen is rapid and temporal. Therefore, an inflammatory response that involves proliferation and maturation of target cells may be restricted to the site of lymphokine production. This inducible hemopoiesis appears to be differentially regulated from the steady state or constitutive hemopoiesis that occurs in the bone marrow microenvironment in the absence of immunological stimuli.

Animals↗

Cell-line specific activation of SV40 transcriptional enhancer by p40tax of HTLV-1.

A transcriptional trans-activator p40tax of HTLV-1 was reported to activate HTLV-1 enhancer, but not SV40 or Rous sarcoma virus enhancer. However, in certain cell lines, we found that SV40 enhancer was activated by p40tax. These cell lines were mostly T cells, where the SV40 enhancer showed only low activity without p40tax. Since p40tax-mediated activation of the LTR is not cell line-specific, the activation of enhancers by p40tax depends on the combination of enhancer and cell type used for the test. Thus, apparent activation by p40tax depends on variable cellular components involved in transcriptional regulation.

Cell Line↗