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Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 361 records · Page 20Linked to original sources

[Lymphokine-activated killer (LAK) adoptive immunotherapy: optimal method for large-scale LAK induction].

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells shows promise as a treatment for malignant disease, but one of the difficult problems associated with the LAK therapy is the method to induce 10(11) to 10(12) of LAK cells. In a study for optimal LAK induction, monocytes separated with counterflow centrifugal elutriation markedly augmented LAK cell induction from lymphocytes in spite of having no cytotoxicity when cultured alone; LAK activity was sufficiently induced from mononuclear cells (MNC) containing approximately 20% of monocytes; LAK activity was induced depending on the serum concentration, and at least 5% of human AB serum in RPMI 1640 was referred to induce optimal LAK activity; and roller bottle was preferable to tube or flask especially at higher MNC density. We concluded that roller bottle with 4 X 10(6) cells/ml of MNC suspended in 1 liter of RPMI 1640 containing 5% AB serum would be the optimal condition for large-scale LAK induction, and administration of LAK cells on the 3rd and 4th day of culture is favorable for weekly performance of LAK adoptive therapy.

Cell Separation↗

[Radiotherapy of nasopharyngeal carcinoma].

The results of irradiation on fifty seven patients with nasopharyngeal carcinoma, treated from 1964 to 1985 at the Shinshu University Hospital, were studied. Forty-two percent of the patients had T3-4 primaries and 68% had N1-3 regional nodes; 86% had Stages III-IV of the disease. Of the 57 patients, 32 had squamous cell carcinomas, and 25 had lymphoepitheliomas. The overall 5-year survival rate was found to be 57%. Primary size (T) and histology influenced the survival of patients; the 5-year survival rate was 70% for T1-2 primary and 39% for T3-4 primary, and 39% for squamous cell carcinoma and 80% for lymphoepithelioma.

Adolescent↗

Synergism of recombinant human interferon gamma with liposome-encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes.

Freshly isolated human peripheral blood monocytes from healthy volunteers are not cytotoxic to allogeneic A375 melanoma cells, but they were rendered tumoricidal by incubation in vitro with either liposomes containing 5 micrograms/mumol phospholipid of muramyl tripeptide phosphatidylethanolamine (liposome-MTP-PE; optimal dose, 500 nmol/ml) or recombinant human interferon gamma (rIFN-gamma; optimal dose, 100 U/ml). A combination of sub-threshold concentrations of liposome-MTP-PE (50 nmol/ml) and rIFN-gamma (1 or 10 U/ml) also induced significant tumor-cell killing, indicating that the effects of rIFN-gamma and liposome-MTP-PE in monocyte activation are synergistic. In contrast to rIFN-gamma, recombinant IFN-alpha and IFN-beta had additive effects with liposome-MTP-PE in human monocyte activation. Since recombinant human IFN-gamma has a synergistic effect with liposome-MTP-PE in monocyte activation, unlike IFN-alpha or IFN-beta, and liposome-MTP-PE as well as rIFN-gamma is available at standardized concentrations, this combination could be of clinical value in the treatment of disseminated malignant disease.

Acetylmuramyl-Alanyl-Isoglutamine↗

Comparative analysis of the priming effect of human interferon-gamma, -alpha, and -beta on synergism with muramyl dipeptide analog for anti-tumor expression of human blood monocytes.

Freshly isolated human peripheral blood monocytes from healthy volunteers were not cytotoxic to allogeneic A375 melanoma cells, but they were activated to the cytotoxic state by incubation in vitro with either des-methyl muramyl dipeptide (norMDP; minimal effective dose, 0.5 micrograms/ml) or recombinant human interferon-gamma (rIFN-gamma; minimal effective dose, 1 U/ml). A combination of subthreshold concentrations of these agents (norMDP, 0.5 micrograms/ml; rIFN-gamma, 10 U/ml) also induced significant cytotoxicity, indicating that the effects of norMDP and rIFN-gamma in monocyte activation are synergistic. Natural human IFN-gamma (nIFN-gamma) and norMDP also had similar synergistic effects. Pretreatment of rIFN-gamma with anti-IFN-gamma antibody completely inhibited its synergistic effect with norMDP in monocyte activation. Because pretreatment of rIFN-gamma and norMDP with polymyxin B did not interfere with their effects in monocyte activation, the preparations were not contaminated with lipopolysaccharide. Moreover, because pretreatment of monocyte monolayers with anti-Leu-11b antibody (anti-natural killer (NK) cell antibody) and complement did not interfere with the synergistic effects of norMDP and rIFN-gamma, whereas pretreatment with anti-Leu-M1 antibody (anti-monocyte antibody) caused complete inhibition of their effects, the observed tumor cytotoxicity of monocyte-rich monolayers was probably not due to a small number of adherent NK cells, but to the stimulation of the monocytes. Natural and recombinant IFN-alpha and IFN-beta at concentrations of greater than or equal to 100 U/ml also induced tumoricidal activity of monocytes, but unlike IFN-gamma, their effects were additive with norMDP, and they had less priming effect than IFN-gamma when they were added before norMDP to monocytes. These findings suggest that recombinant human IFN-gamma has much more synergistic potential with norMDP than IFN-alpha or IFN-beta, and this synergism of rIFN-gamma and norMDP for monocyte activation could be of clinical value in treatment of disseminated malignant diseases, because these compounds are readily available at standardized concentrations.

Acetylmuramyl-Alanyl-Isoglutamine↗

Ultrasonography of mediastinal teratoma.

We have studied real-time sonograms of 11 surgically proven benign mediastinal teratomas. Eight cystic teratomas were sonographically visualized as various kinds of masses: four complex, two solid, and two cystic. The echo patterns of cystic teratomas were determined by the serous or nonserous nature of the cysts. In the presence of serous fluid, the tumor was visualized as a cystic mass. If, on the other hand, the cyst of the tumor was nonserous or was sebaceous, it appeared as a solid or complex tumor. The remaining three solid teratomas, which had some small cysts, appeared as complex tumors.

Adult↗

Activation of antitumor properties in alveolar macrophages from protein-calorie malnourished rats.

Protein-calorie malnutrition (PCM) was induced by feeding male F344 rats on a 5% casein diet for 7 weeks. At appropriate times, rats from control (20% casein diet) and PCM groups were killed and alveolar macrophages (AM) were obtained by bronchoalveolar lavage. The functional integrity of the AM was determined by measuring their ability to become tumoricidal on treatment with macrophage activators, such as muramyl dipeptide (MDP) or multilamellar liposomes containing MDP or its lipophilic analog, MTP-PE. After 5 and 7 weeks, the numbers of lavaged AM per gram body weight of rats were much higher in the PCM group than in the control group. In week 3, AM from the PCM group showed spontaneous tumoricidal activity against syngeneic tumor cells, but in weeks 5 and 7 they did not. However, AM from PCM rats behaved the same way as controls in their response to activation stimuli in vitro with multilamellar liposomes containing synthetic MDP or MTP-PE. These data show that PCM affects the number of AM, but that AM from rats in a state of PCM become tumoricidal in response to activation stimuli in vitro.

Acetylmuramyl-Alanyl-Isoglutamine↗

Potentiation of direct antitumor cytotoxicity and production of tumor cytolytic factors in human blood monocytes by human recombinant interferon-gamma and muramyl dipeptide derivatives.

We investigated whether human peripheral blood monocytes isolated by centrifugal elutriation from healthy donors could be activated to become tumoricidal and release tumor cytolytic factor (TCF) subsequent to incubation with recombinant human interferon-gamma (r-IFN-gamma) or a derivative of muramyl dipeptide (nor-MDP), or both. Blood monocytes incubated in endotoxin-free medium containing up to 1000 U/ml of r-IFN-gamma or in medium containing less than 1 microgram/ml of nor MDP were not activated to lyse radiolabeled allogeneic human tumor cells. In contrast, the incubation of monocytes with various dose combinations of r-IFN-gamma and nor-MDP generated significant direct cytotoxic activity as well as production of TCF. Preincubation of the r-IFN-gamma and nor-MDP mixture with polymyxin B did not inhibit the synergism, thus ruling out the possibility that the process was due to endotoxin contamination. TCF harvested from monocyte culture supernatants was cytolytic against five allogeneic tumor targets, but not against a nontumorigenic cell line. Collectively, the data demonstrate that r-IFN-gamma can prime human blood monocytes to allow their activation by synthetic nor-MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

A dried preparation of liposomes containing muramyl tripeptide phosphatidylethanolamine as a potent activator of human blood monocytes to the antitumor state.

Studies were performed on the activation of human blood monocytes to the antitumor state by a dried preparation of multilamellar vesicle (MLV) liposomes in which synthetic muramyl tripeptide phosphatidylethanolamine (MTP-PE) was inserted directly into the liposome membrane. Dried liposomes composed of synthetic phospholipids [phosphatidylcholine (PC) and phosphatidylserine (PS) in a molar ratio of 7:3] were prepared by lyophilization. Dried liposome-MTP-PE was found to be superior in several ways to free desmethyl muramyl dipeptide (norMDP) or conventional liposome-MTP-PE, prepared immediately before use. First, dried liposome-MTP-PE was stable and strongly activated monocytes when stored for over 3 months in a freezer at -20 degrees C or even in suspension at 4 degrees C. Second, human monocytes in suspension, as well as in the adherent form, were activated to the tumoricidal state by interaction for at least 4 h with the dried preparation of liposome-MTP-PE. Third, monocytes activated with the dried liposome-MTP-PE or conventionally prepared liposome-MTP-PE maintained their tumoricidal activity for a longer period (4 days) than those activated with free norMDP. These results indicate that the dried preparation of liposome-MTP-PE can be stored for a long time, has a reproducible effect that can be standardized and should be valuable for in situ activation of human monocytes to the tumoricidal state, which is associated with eradication of cancer metastases.

Acetylmuramyl-Alanyl-Isoglutamine↗

Scintiscanning demonstration of thymoma: comparative study on scintiscans using 201Tl, 67Ga and 75Se.

Thymus scintigraphy was performed using 201Tl-chloride, 67Ga-citrate and 75Se-selenomethionine on 30 thymoma patients with or without myasthenia gravis. Mass negativity was observed in 6 out of 17 (35.3 per cent) and 3 out of 13 cases (23.1 per cent), respectively. A rate of 70 per cent (21 cases out of 30) of mass positivity was observed by thymus scan using 201Tl. With regard to the relation between thymus scan and cell type, 201Tl-scan exhibited a high rate of mass positivity, regardless of the cell type while the 75Se-scan showed a trend toward mass positivity in epithelial cell predominant cases. With 201Tl, mass positivity was observed when the CPM/g ratio for tumors and blood exceeded 3.0. This trend can serve as an index for the suitability of supplementary chemo- and radiotherapies, as well as for prognosis in cases of relapse, and in those for whom excision was not complete.

Gallium Radioisotopes↗

A clinical trial of interferon therapy in a case of rapidly progressive SSPE.

A 6-year-old Japanese boy with rapidly progressive SSPE was reported, who received interferon therapy and recovered from stage III-A to stage II-B according to the criteria of Freeman. This is the first report of the beneficial therapeutic effect of interferon therapy on rapidly progressive SSPE, which is lethal and poorly responded to any kind of previous therapeutic trials.

Child↗

Respiratory diseases in hard metal workers: an occupational hygiene study in a factory.

A hygiene study of a hard metal factory was conducted from 1981 to 1984. All workers exposed to hard metal were medically examined and their exposure to cobalt measured. Eighteen employees had occupational asthma related to exposure to hard metal, a prevalence rate of 5.6%. Nine had a positive bronchial provocation test to cobalt and reactions of the immediate, late, or dual type were elicited. Exposure measurements suggest that asthma may be caused by cobalt at a mean time weighted average concentration below 0.05 mg/m3. Only two of the nine individuals with cobalt asthma had a positive patch test to cobalt. Chest radiographs of three workers showed diffuse shadows of category 1 or over. X ray microanalysis of lung biopsy specimens from two of these three workers showed the presence of tungsten, titanium, cobalt, nickel, and some minerals. One of the two was diagnosed as having pneumoconiosis due to exposure to silica in a steel industry and the other was suspected of having pulmonary fibrosis caused by dust generated from the carborundum wheels used to grind hard metal. There were no cases with interstitial pneumonitis in the factory.

Adult↗

Antitumor and phagocytic activities of rat alveolar macrophage subpopulations separated on a discontinuous gradient of bovine serum albumin.

Alveolar macrophages (AM) lavaged from the lungs of normal F344 rats were separated on a discontinuous density gradient of bovine serum albumin (BSA) into four fractions designated as fraction A (20/25% BSA interface), fraction B (25/30%), fraction C (30/35%); and fraction D (35%/pellet). The abilities of these four fractions to form rosettes with opsonized sheep red blood cells (SRBC), to phagocytize these SRBC, and to become tumoricidal in response to macrophage-activating agents in vitro were examined. Fractions A and D had greater abilities than fractions B and C to form rosettes and to phagocytize opsonized SRBC, and a good correlation was found between these two activities in the four fractions. In contrast, the four AM fractions were equally susceptible to activation stimuli, such as lipopolysaccharide (LPS), Nocardia rubra cell wall skeleton (N-CWS), macrophage activating factor (MAF), muramyl dipeptide (MDP), or a mixture of MAF and MDP in vitro to become cytotoxic to syngeneic mammary adenocarcinoma cells.

Animals↗