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Biomedical subjects

G Peri

Publications and source records attributed to G Peri.

At least 91 records · Page 5Linked to original sources

Role of endotoxin in the expression of human monocyte cytotoxicity.

The role of bacterial endotoxin in the expression of human monocyte cytotoxicity was studied. Endotoxin contamination of all reagents and steps of the experimental procedure were assessed by the limulus amebocyte lysate (LAL) assay. Peripheral blood monocytes were separated by adherence, and cytotoxicity was measured as [3H]-thymidine release from prelabeled mKSA-TU5 murine target cells in a 48-hr assay. Human monocytes expressed appreciable levels of spontaneous cytotoxicity under LAL- conditions irrespective of the serum source employed (LAL- or LAL+ fetal bovine serum, FBS, or LAL- human cord serum, HCS). HCS gave the highest cytotoxicity levels and LAL- FBS the lowest. Polymyxin B (10 micrograms/ml), which inhibited endotoxin-induced gelation of LAL and activation of mononuclear cells for procoagulant activity, did not affect the expression of spontaneous monocyte cytotoxicity with all three sera used. Three preparations of endotoxin used in the present study (Escherichia coli, S. typhosa, S. minnesota) caused small increases in monocyte killing in micrograms per milliliter concentrations only in 5 of 19 experiments performed. Human lymphoblastoid interferon (LAL-) and phytohemagglutinin-elicited lymphokine supernatants (LAL-) enhanced the tumoricidal activity of human monocytes under LAL- conditions and were not affected by Polymyxin B. It is concluded that exposure to endotoxin is not a prerequisite for the expression of spontaneous cytotoxicity by human blood monocytes.

Animals↗

Generation of procoagulant activity by mononuclear phagocytes: a possible mechanism contributing to blood clotting activation within malignant tissues.

This study investigated the procoagulant activity (PCA) of mononuclear phagocytes from rabbits bearing the V2 carcinoma. Macrophages harvested from either intraperitoneally or subcutaneously growing tumors were found to express a very strong procoagulant activity as compared with peritoneal macrophages and circulating mononuclear cells from the same animals. On the other hand, when incubated with or without endotoxin in short-term cultures, circulating mononuclear cells from tumor-bearing animals generated significantly more procoagulant activity than those from control animals. In all instances, procoagulant activity was identified as tissue factor by using assay systems with plasmas selectively deficient in the various clotting factors. These results indicate that, besides cancer cells, mononuclear phagocytes might also play an important role in the activation of blood coagulation and in the deposition of fibrin at the host-tumor interface.

Animals↗

In vitro and in vivo cytotoxicity of 6 amino-5-formyl-methylamino-1,3-dimethyl uracil, a uracilic metabolite of caffeine.

The in vitro cytotoxicity of 6 amino-5 formylmethylamino-1,3 dimethyluracil (ADMU) a major metabolite of caffeine in rats was studied by cell counts or [3H]thymidine incorporation in the murine Lewis lung carcinoma (3LL) and L929 fibroblast cells and in the human E cell line derived from an ovarian carcinoma. Unlike 5-fluorouracil (5FU) which was markedly cytotoxic, ADMU concentrations up to 60 micrograms/ml were devoid appreciable cytocidal action. Similarly, 1-10 micrograms 5FU markedly inhibited the blastogenic response of rat lymphocytes to PHA, whereas lymphoproliferation was not affected at ADMU concentrations up to 100 micrograms/ml. In vivo administration of ADMU (40 mg/kg, twice a day on day 1 to 3) to L1210 leukaemia-bearing mice caused a transient short-lasting reduction of tumour cell numbers only on day 6 after leukaemia inoculation.U

Animals↗

Proximal gastric vagotomy and anterior fundoplication as complementary procedures to Heller's operation for achalasia.

While Heller's myotomy has become the accepted operation for achalasia, still, there is no agreement about the indications for and choice of complementary procedures to minimize subsequent acid esophageal reflux. In the instances described in this investigation Heller's operation was accompanied by proximal gastric, or highly selective, vagotomy and anterior fundoplication. Dysphagia was abolished and normal alimentation restored in all but one patient, who was elderly and had an advanced megaesophagus. In every patient after the operation, results of pH-manometry, acid reflux tests and endoscopy demonstrated the absence of both acid reflux and esophagitis.

Adolescent↗

Antibody-dependent and -independent cytotoxicity of human mononuclear phagocytes: defective stimulation of tumoricidal activity in milk macrophages.

Human peripheral blood monocytes, milk macrophages and peritoneal exudate macrophages were purified by adherence. antibody-dependent cellular cytotoxicity (ADCC) was measured using the murine TLX9 lymphoma pre-labelled with 3H-thymidine. Direct, antibody-independent tumoricidal activity was measured against the murine TU5 line pre-labelled with 3H-thymidine. All mononuclear phagocyte populations tested were similarly effective in mediating ADCC against TLX9 cells. In the absence of deliberate stimulation blood monocytes and peritoneal macrophages had appreciable spontaneous cytotoxicity against the susceptible TU5 line. In contrast, four out of 10 milk macrophage preparations lacked detectable spontaneous killing activity on this target. In vitro exposure to partially purified fibroblast interferon (IFN) or to lymphokine supernatants from PHA stimulated lymphocytes augmented the direct tumoricidal activity of blood monocytes and peritoneal exudate macrophages. Milk macrophages were completely unresponsive to IFN and lymphokines. therefore the capacity to mediate antibody-dependent and -independent cytotoxicity against tumour cells can be dissociated to some extent in human mononuclear phagocyte populations from diverse anatomical sites.

Animals↗

Tumoricidal activity of macrophages isolated from human ascitic and solid ovarian carcinomas: augmentation by interferon, lymphokines and endotoxin.

Peripheral blood monocytes and macrophages from ascitic or solid tumors were obtained from 50 patients with advanced (Stage III or IV) ovarian carcinoma. Blood monocytes and peritoneal macrophages from 76 patients undergoing surgery for benign gynecological diseases were used as controls. Macrophages were 30% (range 0.2-6.2) and 2% (range 0.2-4) of mononuclear cell suspensions from ascitic and solid tumors, respectively. Cytolytic activity was measured as release of [3H]-thymidine from prelabelled mKSARU5 (TU5) target cells at an effector to target cell ratio of 20:1. Peripheral blood monocytes and tumor-associated macrophages had baseline cytotoxicity lower than or similar to that of control peripheral blood and peritoneal macrophages respectively. In vitro exposure to partially purified human fibroblast interferon, lymphokine supernatants or endotoxin augmented the cytotoxicity of mononuclear phagocytes, and no significant difference was observed between control and ovarian cancer effector cells from peritoneal effusions. In four patients, macrophages were isolated from the solid tumor or from the malignant effusion and tested in parallel: in two out of four subjects, macrophages from the solid neoplasm showed defective cytotoxicity compared to ascites effector cells from the same subject. When primary ovarian carcinoma cultures were used as targets, tumor cells from two out of five patients tested were relatively resistant to activated macrophage cytotoxicity. Thus, tumor-associated macrophages from ascitic or solid ovarian neoplasms showed no evidence of activation, in terms of spontaneous cytotoxicity or responsiveness to stimuli: it appears unlikely that small numbers of non-activated macrophages present within primary ovarian carcinomas act as a significant mechanism of restraint of neoplastic growth, at least at this anatomical site.

Ascitic Fluid↗

A modified 'low pH' lignocaine method to isolate human monocytes: a comparison with other separation procedures.

A modified 'low pH' lignocaine method for the recovery of human monocytes from untreated plastics is described and compared with other adherence separation procedures, viz. mechanical scraping by a rubber policeman, microexudate-coated plastic method and pretreatment of plastics by the fetal calf serum (FCS). Monocytes separated by each of the above-mentioned techniques carried out in parallel were characterised by morphological and functional criteria: non-specific esterase staining, contamination by T- and B-lymphocytes, viability, adherence, neutral red uptake, phagocytosis of yeast particles, random mobility, chemotaxis, and tumoricidal activity both in the absence and in the presence of interferon and lymphokines. The 'low pH' lignocaine method appears to be a simple and reproducible technique for the isolation of human monocytes. It seem preferable to other adherence procedures inasmuch as it yields viable, pure and functionally intact monocytes without requiring preconditioned plastics.

Blood↗

Fractures of the frontal sinus.

Fractures of the frontal sinus are frequently seen in patients with cranio-facial injuries. Trauma to the posterior wall and more deeply located tissues: anterior fossa, dura and brain, give an indication of the seriousness of such injuries. We point out some particular aspects of our experience; in the neurosurgical approach to such lesions; we use a classification based on treatment: -when the posterior wall of the sinus is not, or only slightly damaged, we drain it using a thin suction catheter pulled through the fronto-nasal duct, kept in place for six to ten days. -when a comminuted fracture of the frontal arch occurs in the sinus area, a large cortico-cancellous onlay bone graft is used to rebuild a harmonious frontal contour and avoid the risk of secondary deformity.

Adolescent↗

The use of a single fronto-zygomatic osteosynthesis plate and a sinus balloon in the repair of fractures of the lateral middle third of the face.

In certain orbito-zygomatic fractures, a fronto-zygomatic screwed plate and a sinus balloon permit, at the expense of a single eyebrow incision, the repositioning of the cheekbone and the alignment of the other fracture sites; the other fractures sites consolidate and remodel themselves spontaneously due to the action of the adjacent soft tissues. The plate is malleable so that correct reduction can occur during the course of surgical repair; the plate should align the cheekbone perfectly. Neglect of the stability offered by reduction after exposure of the bone fragments may seem exaggerated, in simple cases; the orbital approach is without risk and limited. This argument - which also depends on the experience of the surgeon - does not apply in the case with a comminution of the orbital rim; closed fracture site reduction and distant osteosynthesis offer an alternative to the classical repair which requires a wide cutaneous incision and significant periosteal stripping with the subsequent risk of eyelid distortion.

Bone Plates↗

Cytotoxicity of human peripheral blood monocytes against Trichomonas vaginalis.

Human peripheral blood monocytes were purified by adherence on microexudate-coated plastic and detached by exposure to 1 mM ethylenediamine tetracetic acid. Lysis of Trichomonas vaginalis was measured as release of 3H-thymidine from prelabelled protozoa after 48 hr of incubation. Human blood monocytes had appreciable levels of spontaneous cytotoxicity against Trichomonas vaginalis at effector-to-target cell ratios ranging from 3:1 to 25:1. Cytotoxicity was expressed with fetal bovine serum and human AB serum. Unseparated mononuclear cells, containing 10-25% monocytes as assessed by staining with non-specific esterase, were significantly cytotoxic against Trichomonas vaginalis but cytolysis levels were lower than those of purified monocytes. Lymphoid cells depleted of adherent cells by repeated incubations on plastic (less than 2% esterase-positive cells) had little cytotoxicity against these protozoa. In vitro exposure to silica natural 40-75% inhibition of the cytotoxic capacity of monocytic preparations. The natural cytotoxic capacity of human monocytes against Trichomonas vaginalis could represent one line of resistance against these protozoa.

Adult↗

Cytotoxicity on tumor cells of peripheral blood monocytes and tumor-associated macrophages in patients with ascites ovarian tumors.

Mononuclear phagocytes were isolated from the peripheral blood (PB) and ascites tumors of 35 patients with epithelial ovarian tumors. After 48 hours of incubation with the TU5 tumor, tumor-associated macrophages (TAM) and PB monocytes from cancer patients showed lower cytolytic activity than did control cells, but by 72 hours there was little difference between control and ovarian cancer effector cells. Primary ovarian carcinoma cultures were heterogeneous in their susceptibility to macrophage cytotoxicity. Tumor cells from 7 patients were significantly lysed by monocytes and macrophages, whereas four ovarian cancer cell preparations were resistant to cytotoxicity. A "feeding" effect of mononuclear phagocytes on non-lysable tumor cells was detected in terms of both lower [3H]thymidine-release values in the cytolysis assay and increased proliferation in cytostasis assays. Thus patients with ovarian carcinomatous ascites PB monocytes and TAM had impaired cytotoxicity against a tumor cell line, and primary ovarian carcinoma cultures were heterogeneous in their interaction with mononuclear phagocytes.

Adenocarcinoma↗

Natural cytotoxicity on tumour cells of human macrophages obtained from diverse anatomical sites.

Human mononuclear phagocytes were isolated from peripheral blood, peritoneal exudate and early lactation milk by adherence on microexudate-coated plastic and exposure to ethylene diamine tetracetic acid. Their cytolytic activity was measured as 3H-thymidine release from prelabelled target cells over 48-72 hr and cytostasis was evaluated in a spectrophotometric 72-hr assay. The murine SV40-transformed mKSA-TU5 line and the human E cell line, derived from an ovarian carcinoma, were employed as targets. Peripheral blood monocytes, in vitro-matured monocyte-derived macrophages, peritoneal macrophages and milk macrophages were all significantly cytolytic and cytostatic on these target cells at attacker to target cell ratios ranging from 5:1 to 40:1. When monocytes were cultivated in vitro, no loss of cytocidal capacity occurred over the first 10 days of culture, whereas later on, when epithelioid and giant cells predominate in the cultures, mononuclear phagocytes had little cytotoxic activity. Adherent cells obtained from cord blood or from the peripheral blood of old donors had natural cytotoxicity similar to monocytes obtained from young adult volunteers. Peripheral blood monocytes and peritoneal macrophages showed enhanced cytolytic activity after exposure to partially purified human fibroblast interferon. These experiments suggest that in the human mononuclear phagocyte series cytotoxicity on tumour cells is not restricted to circulating monocytes but is also expressed by macrophages obtained from diverse anatomical sites.

Adult↗

Cytotoxicity on tumour cells of human mononuclear phagocytes: defective tumoricidal capacity of alveolar macrophages.

Human cells of the monocyte-macrophage lineage were isolated by adherence from peripheral blood, peritoneal exudate, non-neoplastic ascites, benign ovarian cystic fluid and bronchoalveolar lavages. Cytolytic activity was measured as 3H-thymidine release from prelabelled mKSA TU5 tumour cells over 48-72 hr and cytostasis was evaluated in a 72-hr spectrophotometric assay. Mononuclear phagocytes from the various anatomical sites examined, except lung alveolar spaces, were significantly cytolytic and cytostatic on target cells. Unlike other cells of the monocyte-macrophage lineage, alveolar macrophages were not cytocidal, but significantly inhibited tumour cell proliferative capacity. Peripheral blood monocytes and peritoneal macrophages showed enhanced cytotoxicity in the presence of partially purified human fibroblast interferon or of lymphokine supernatants from mitogen-stimulated lymphocytes. In contrast, interferon did not affect the cytotoxic potential of alveolar macrophages, whereas lymphokines augmented their cytostatic activity and rendered them weakly cytolytic.

Adult↗