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Biomedical subjects

A Okubo

Publications and source records attributed to A Okubo.

At least 19 recordsLinked to original sources

Intraocular manifestations of systemic sarcoidosis.

The incidence of intraocular manifestations was studied in 159 patients with systemic sarcoidosis. Eighty-seven patients (54.7%) who presented ocular lesions suggestive of sarcoidosis as an initial manifestation were diagnosed after a systemic survey. Seventy-two patients (45.3%) had chest signs or symptoms and were referred to ophthalmic examination during a diagnostic survey. Of the 159 patients, 126 (79.2%) showed intraocular involvements at diagnosis. In these patients with ocular involvements, iritis was the most frequent lesion, being seen in 74.7%. Gonioscopic examinations revealed trabecular nodules and tent-like peripheral anterior synechia in 61.2 and 54.5% of the patients respectively. Retinal perivasculitis and spotty retinochoroidal exudates were seen in 67.3 and 53.9% of the patients respectively. The data indicated the presence of intraocular lesions in a significant number of patients with sarcoidosis. These findings emphasize that all patients with systemic sarcoidosis need a thorough eye examination. This ocular examination should include gonioscopy.

Adolescent

[De novo retinal break associated with excessive cryotherapy].

Three patients who had been treated with transscleral cryotherapy for retinal breaks and associated retinal detachment developed de novo retinal breaks and/or retinal thinning at the site of cryotherapy in the early postoperative period. Additional surgical interventions were required because retinal detachment had extended or remained unchanged postoperatively. We think that this may be due to excessive cryotherapy and is an early postoperative complication transscleral cryotherapy that to our knowledge has not previously been reported. This would suggest that when performing cryotherapy for retinal breaks and associated retinal detachment, care should be taken not to treat excessively.

Adult

Odontogenic epithelial hamartoma of the gingiva: a case report.

A rare case of odontogenic epithelial hamartoma of the gingiva in a 63-year-old Japanese female is reported. This tumor-like lesion probably originated from the reduced tooth-forming tissues such as rests of dental lamina lying dormant in the gingiva after odontogenesis. The differential diagnosis of this lesion from many other odontogenic and glandular tumors is important; however, through careful clinico-pathological examinations, it would not be a very difficult task.

Connective Tissue

[An elderly case of small cell lung cancer showing a good partial response by chronic daily administration of oral etoposide].

An 86-year-old man was admitted to our hospital with complaints of dyspnea and productive cough, and diagnosed as small cell lung cancer with sputum cytology. We concluded that he was unsuitable for standard aggressive intravenous chemotherapy because of an old age, a poor performance status and cardiac complication. He was treated with oral etoposide (100 mg/day x 16.5 days), and showed a good partial response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia, and anorexia. Daily oral administration of etoposide is considered to be effective and useful for elderly patient with small cell lung cancer.

Administration, Oral

[Measurement of anti-microsomal and anti-thyroglobulin antibodies by radioimmunoassay].

In this study, we measured anti-microsomal (same as anti-thyroid peroxidase) and anti-thyroglobulin antibodies (anti-TPOAb and anti-TgAb) in sera by new RIA kits and compared with the conventional particle agglutination (PA) kits. Two of 80 normals (2.5%) showed anti-TPOAb positive activity (greater than or equal to 0.3 unit/ml), and 9 of same samples (11.3%) showed anti TgAb positive activity (greater than or equal to 0.3 unit/ml). Sixty of 67 patients with Graves' disease (89.6%), and 14 of 22 with Hashimoto's disease (63.6%) were anti-TPOAb positive, and 42 (62.7%), and 18 (81.8%) were anti-TgAb positive respectively. Samples of 5 non-autoimmune disease were all negative by TPOAb and TgAb assays, suggesting the high specificity of new RIA kits to the autoimmune thyroid diseases. The RIA and PA methods showed a good correlation (anti-TPOAb:rs = 0.9134, anti-TgAb:rs = 0.7016). However, several negative sera in PA assay showed positive values in the RIA, so it was showed that new RIA kits were more sensitive than the PA assays.

Autoantibodies

Heterogeneity in responses of human blood monocytes to granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has stimulatory effects on various monocyte functions. We examined whether all or only some blood monocytes could respond to GM-CSF. Monocytes from peripheral blood of healthy donors were separated by size into five fractions by counter-flow centrifugal elutriation (CCE). The phagocytic activities of monocytes in these fractions depended on the size of the cells. On activation by bacteria-derived stimuli, these fractions showed similar responses of production of monokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) and cytotoxicity against allogeneic tumor cells. On treatment of these fractions with optimal concentration of GM-CSF, fractions 3, 4, and 5 showed tumoricidal activity and produced cell-associated IL-1, fraction 3 producing the most, whereas release of IL-1 and TNF in the supernatant was not observed. The cell-associated IL-1 was identified as IL-1 alpha, not IL-1 beta, by neutralizing tests with antisera against IL-1 alpha and IL-1 beta. GM-CSF also induced the proliferative and colony-forming responses of medium and large monocytes. These observations suggest that adoptive therapy with macrophage progenitor cells in peripheral blood may be useful in combination with GM-CSF for treatment of monocytopenia after chemotherapy or radiation therapy.

Cell Division

Tumor cytotoxicity and interleukin 1 production of blood monocytes of lung cancer patients.

The effects of lung cancer on the abilities of blood monocytes to produce interleukin-1 and to mediate antitumor activity were examined. The functional integrity of blood monocytes was determined by their capacity to respond in vitro to a variety of activating agents and become tumoricidal, as assessed by a radioactive release assay and ability to produce interleukin-1 in vitro. The results show that the presence of lung cancer significantly increased the number of harvested blood monocytes and that the spontaneous tumoricidal activity of these monocytes was slightly high as compared to monocytes obtained from healthy donors. The production of interleukin-1 by monocytes of healthy donors and lung cancer patients was similar. Blood monocytes obtained from lung cancer patients were less cytotoxic against allogeneic A375 melanoma cells as compared with those of healthy donors subsequent to incubation with a soluble muramyl dipeptide analog or lipopolysaccharide, but were as tumoricidal as those from healthy donors when activated with lipophilic muramyl tripeptide (MTP-PE) entrapped in multilamellar liposomes. The finding that monocytes of patients with lung cancer can respond to MTP-PE encapsulated in liposomes, recommends the use of these liposomes in therapy of human lung cancer.

Acetylmuramyl-Alanyl-Isoglutamine

Production of tumor necrosis factor-alpha by alveolar macrophages of lung cancer patients.

The abilities of human alveolar macrophages (AM) obtained from healthy donors and patients with lung cancer to produce tumor necrosis factor (TNF) were compared with those of their blood monocytes after activation with lipopolysaccharide (LPS). TNF activity was assayed by measuring cytotoxicity against actinomycin D-treated L929 cells and TNF was determined quantitatively by sandwich enzyme-linked immunosorbent assay (ELISA) with polyclonal and monoclonal antibodies against TNF-alpha. Unstimulated AM from healthy donors released variable amounts of TNF spontaneously, whereas blood monocytes did not. When treated with LPS for 24 h, AM and monocytes produced TNF dose-dependently, but TNF production by AM was significantly more than that by blood monocytes. This TNF activity was inhibited completely by monoclonal anti-TNF-alpha antibody. Macrophages generated by in vitro maturation of monocytes induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) produced more TNF than freshly isolated monocytes. No difference was found in the abilities of AM from healthy donors and patients with lung cancer to produce TNF after activation stimuli. These observations suggest that human AM may be important in in vivo antitumor defense of the lung through TNF-alpha production.

Adult

Suppression by interleukin 4 of activation of human blood monocytes to the tumoricidal state.

The effect of interleukin 4 (IL-4) on expression of antitumor activity of blood monocytes purified by counter-flow centrifugal elutriation from healthy donors was examined. The blood monocytes were incubated for 24 h in medium with lipopolysaccharide, interferon gamma (IFN-gamma) or desmethyl muramyl dipeptide (norMDP) or with IFN-gamma and norMDP in the presence of IL-4, and then their tumoricidal activity was assayed by measuring 125IUdR release from human melanoma (A375) cells. Irrespective of activation stimulus, addition of IL-4 to cultures of monocytes and activators resulted in dose-dependent suppression of the tumoricidal activity of monocytes against parent A375 melanoma cells and the variant cells, A375-R resistant to IL-1 and tumor necrosis factor alpha. IL-4 suppressed the early induction phase of monocyte activation. Rabbit anti-IL-4 antisera completely blocked the IL-4-mediated suppression of monocyte activation to the tumoricidal state. These findings suggest that IL-4 is important in vivo in down-regulation of anti-tumor expression of monocytes.

Cells, Cultured

Decrease of lymphokine (interleukin-2)-activated killer activity in peripheral blood after administration of natural interferon-gamma.

Interferon-gamma (IFN-gamma) acts on a large array of different types of cell and has potent immunomodulatory activities besides cytotoxic effects on tumors. In a phase I study, some immunologic parameters of blood mononuclear cells from healthy volunteers who received intramuscular injections of natural human IFN-gamma were analyzed. The percentage of Leu-11a positive cells, natural killer (NK) activity, lymphokine (interleukin-2)-activated killer (LAK) activity and monokine production were measured either in blood mononuclear cells or in purified samples of lymphocytes or monocytes of the donors before and 24 h after IFN-gamma injection. After IFN-gamma injection, the percentage of Leu-11a positive cells and the LAK activity in the blood were significantly reduced, but NK activity and monokine production remained unchanged. These findings suggest that in vivo IFN-gamma acts directly or indirectly on Leu-11a positive cells and reduces LAK activity by changing the recruitment of LAK precursors in the blood.

Burkitt Lymphoma

Vitreous as tamponade in healing of rhegmatogenous retinal detachment.

The condition of the vitreous body was assessed by a photographic method after surgical treatment in 116 patients with rhegmatogenous retinal detachment showing horseshoe-shaped retinal breaks. The condition was classified into three groups: 1) the cortical vitreous covered the retinal break under both static and kinetic conditions (complete type), 2) the cortical vitreous covered the break only under the static condition (incomplete type), and 3) the break was not covered by the cortical vitreous (uncovered type). The success rate of the primary surgery was 100% in both the complete and incomplete types, but it was 58% in the uncovered type, where the final success rate after the second surgery was only 89%. The radial retinal folds were found after surgery at a high incidence in the uncovered type. The time required for disappearance of the subretinal fluid was shorter in the complete than in the incomplete type; in the uncovered type it took a long time for the subretinal fluid to diminish. It was concluded that the cortical vitreous served as a tamponade to prevent vitreous fluid flow into the subretinal space, thus facilitating reattachment of the retina.

Adult

On the spatial spread of the grey squirrel in Britain.

We present a diffusion-competition model to describe the interaction between the externally introduced grey squirrel and the indigenous red squirrel in Britain. We estimate the model parameters from field data. Solution of the model predicts waves of grey squirrel invasion with speed of invasion typical of that observed in the field. Numerical solution of the model on a two-dimensional domain gives population distributions qualitatively similar to those observed. We suggest that competition alone could account for the observed displacement of the red squirrel by the grey in large regions of Britain. The solutions are qualitatively similar to those for a single species spreading in the absence of competition. The quantitative difference is because competition slows down the speed of advance of the invading species.

Animals

A case of bronchogenic cyst with high production of antigen CA 19-9.

A 35-year-old man was hospitalized with complaints of retrosternal pain and high fever. A chest radiograph showed a large round mass in the mediastinum. Of the several tumor markers in the serum tested, only CA 19-9 was elevated. Thoracotomy revealed a cystic mass with purulent hemorrhagic materials. Histologically the cyst was lined by bronchial epithelium with no evidence of malignancy. The high level of CA 19-9 in the cystic fluid, and positive immunohistochemical staining of the bronchial glands in the cyst wall for CA 19-9 indicated that the elevated serum level of CA 19-9 originated from the bronchogenic cyst after its infection.

Adult

Inhibition of the infectivity and cytopathic effect of human immunodeficiency virus by water-soluble lignin in an extract of the culture medium of Lentinus edodes mycelia (LEM).

Inhibition of the infectivity and cytopathic effect of human immunodeficiency virus type 1 (HIV-1) by the immunoactive fractions obtained from LEM, which is an extract of the culture medium of Lentinus edodes mycelia, is reported. A purified fraction, EPS4, obtained from LEM by ethanol precipitation followed by hydrophobic chromatography and gel filtration chromatography completely inhibited the HIV-1 induced cytopathic effect in vitro at concentrations of greater than or equal to 10 micrograms/ml. Chemical and spectral analysis revealed that EPS4 is composed of water-soluble lignins containing minor amounts of protein (3.2%) and sugars (12.2%). Taken together with the previously reported observation that EPS4 promotes the activation of macrophages and the proliferation of bone marrow cells, the fraction appears to possess both an immunostimulating activity and an anti-HIV effect in vitro.

Amino Acids

Membrane-associated interleukin 1 alpha as a mediator of tumor cell killing by human blood monocytes fixed with paraformaldehyde.

Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated antitumor monokine(s) in response to activation stimuli such as various types of interferon (IFN) and/or synthetic desmethyl muramyl dipeptide (norMDP). IFNs (alpha, beta, and gamma) and norMDP rendered blood monocytes cytotoxic to allogeneic A375 melanoma cells, as assayed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with any type of IFN for 16 h, and then fixed with paraformaldehyde, they did not show cytotoxicity to A375 cells, but when they were fixed after treatment with norMDP or lipopolysaccharide they showed significant cytotoxicity to A375 melanoma cells. This membrane-associated antitumor monokine induced by the synergistic actions of suboptimal concentrations of IFN-gamma and norMDP, was cytotoxic to HT-29 colon cancer cells as well as A375 melanoma cells, but not to actinomycin D-treated L-929 cells. The fixed monocyte-mediated cytotoxicity against A375 melanoma cells was completely inhibited by a specific anti-interleukin 1 alpha antiserum, but not by a specific anti-interleukin 1 beta antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated interleukin 1 alpha is involved through cell-to-cell contact in the host defense mechanism against cancer.

Acetylmuramyl-Alanyl-Isoglutamine

Tumor cytotoxicity of human monocyte membrane-bound interleukin-1 alpha induced by synergistic actions of interferon-gamma and synthetic acyltripeptide, FK-565.

Human blood monocytes were isolated by counter-flow centrifugal elutriation from healthy donors and these noncytotoxic monocytes were rendered tumoricidal to allogeneic melanoma (A375) cells by activation with a synthetic acyltripeptide (FK-565), as assessed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with FK-565 for 16 h, and then fixed with paraformaldehyde, they showed cytotoxicity to A375 melanoma cells. The fixed-monocyte-mediated cytotoxicity to A375 cells was induced by the synergistic actions of FK-565 and recombinant interferon-gamma (rIFN-gamma), but not other cytokines [rIFN-alpha A, rIFN-beta, tumor necrosis factor (TNF), interleukin (IL)-2, -3 and -6]. For synergistic activation of monocytes with induction of a membrane-associated antitumor monokine, the monocytes had to be incubated first with rIFN-gamma and then with FK-565. FK-565 also acted synergistically with rIFN-gamma to stimulate monocytes to produce membrane-associated IL-1 activity, which induced C3H/HeJ thymocyte blastogenesis in response to phytohemagglutinin P. The tumoricidal and thymocyte-stimulating activities of the fixed monocytes were almost completely inhibited by a specific anti-(IL-1 alpha) antiserum, but not by a specific anti-(IL-1 beta) antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated IL-1 alpha of human blood monocytes can be induced by two activation signals (rIFN-gamma then FK-565) at their suboptimal concentrations.

Antineoplastic Agents

Killing of alveolar macrophages and of monocytes that have responded to granulocyte-macrophage colony-stimulating factor by human lymphokine-activated killer cells.

The susceptibilities of human blood monocytes and alveolar macrophages (AM) to cytotoxicity mediated by lymphokine (IL-2)-activated killer (LAK) cells were examined. Monocytes and AM of healthy donors were obtained by counter-flow centrifugal elutriation (CCE) and bronchoalveolar lavage, respectively. The LAK activity induced by incubation of blood mononuclear cells (MNC) for 4 days with recombinant interleukin 2 (IL-2) was measured by a 4-h 51Cr release assay. The LAK cells were not cytotoxic to freshly isolated monocytes, but were cytotoxic to autologous fresh AM and monocytes that had been incubated for more than 4 days in medium alone. Blood monocytes that had been incubated for 4 days in medium with granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) or interleukin 3(IL-3) were much more susceptible than untreated monocytes to the cytotoxicity of LAK cells. When blood monocytes were separated by CCE into subpopulations of three sizes (small, medium and large), the medium- and large-sized monocytes showed greater responses to GM-CSF in terms of DNA synthesis and colony formation than the small-sized cells. After treatment with GM-CSF for 4 days, these medium and large monocytes were more susceptible than the small monocytes to the cytotoxic action of LAK cells. These results suggest that LAK cells may be important in situ in down-regulating the functions of mature macrophages and blood monocytes that have responded to GM-CSF.

Biological Factors

Normal human alveolar macrophages have more ability than blood monocytes to produce cell-associated interleukin-1-alpha.

Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from healthy donors, and their abilities to produce extracellular and cell-associated interleukin 1 (IL-1) in response to various activation stimuli were compared with those of autologous blood monocytes. The production of IL-1 alpha and IL-1 beta by monocytes and AM was examined by thymocyte co-stimulation assay and enzyme immunoassays (EIA). Results showed that when activated with lipopolysaccharide (LPS) or desmethyl muramyl dipeptide (norMDP), AM released much less extracellular IL-1 beta than did blood monocytes. In contrast, these activated AM produced more cell-associated IL-1 than did blood monocytes. When the IL-1 activity was examined by the thymocyte assay, the extracellular and cell-associated IL-1 produced by the two cell types were largely IL-1 beta and IL-1 alpha, respectively, as shown by antibody neutralization. The cell-associated IL-1 activity of AM induced by the synergistic actions of suboptimal concentrations of recombinant interferon-gamma (rIFN-gamma) and norMDP was also higher than that of autologous blood monocytes. Consistent with these findings on AM, macrophages generated in vitro by maturation of blood monocytes produced higher levels of cell-associated IL-1 activity than did freshly isolated monocytes. These observations suggest that AM may play a critical role in situ regulation of pulmonary inflammatory and immune reactions through production of cell-associated IL-1 alpha.

Adult