Biomedical subjects

R Megirian

Publications and source records attributed to R Megirian.

At least 19 recordsLinked to original sources

PubMed1985

The effects of essential fatty acid deficiency on pulmonary alveolar macrophage function.

Male rats were maintained for periods of up to 16 weeks on a fat free diet which was supplemented with either 4% tripalmitin (essential fatty acid [EFA] deficient) or with 4% safflower oil (SAFF, control). Pulmonary alveolar macrophages (PAM) were obtained by lung lavage. PAM from EFA deficient rats had reduced phagocytic activity and capacity. Intracellular killing of ingested yeast was also reduced by EFA deficiency. The activity of acid phosphatase, beta-glucuronidase and cathepsin D from PAM was not altered by dietary treatment. Transmission electron microscopy failed to show any consistent morphologic differences between PAM from EFA deficient and SAFF animals, but did confirm the decreased phagocytosis by PAM from EFA deficient rats. However, scanning electron microscopy did show loss of pseudopodia in PAM from EFA deficient rats. EFA deficiency was demonstrated by analyzing the methyl esters of the fatty aids from the total lipid extract of PAM. The arachidonate content was decreased while the eicosatrienoate content was increased in PAM derived from rats fed the EFA deficient diet. In an effort to elucidate further the mechanism of action of EFA deficiency in impairing phagocytosis by PAM, inhibitors of various reactions which lead to oxygenated derivatives of arachidonate were studied using PAM from chow fed rats. Some of these inhibitors were effective in diminishing phagocytosis. Furthermore, PAM from these preparations when fixed in suspension and examined with scanning electron microscopy showed morphological changes similar to those seen in EFA deficiency. This similarity of surface ultrastructural changes suggests that EFA deficiency may impair phagocytic function of PAM by reducing availability of an oxygenated derivative of arachidonic acid.

Acid Phosphatase↗

PubMed1984

Biochemical and functional alterations in macrophages after thermal injury.

Biochemical and functional measurements of rat pulmonary alveolar macrophages were measured 4 h after 1 10-s, 26 to 28% total body surface area, full-thickness scald burn induced under ether anesthesia. Both phagocytic activity and capacity were significantly decreased to a comparable extent, whereas microbicidal activity was increased almost twofold in macrophages from the burned animals. Concurrent with the decreased phagocytic function was a marked impairment in chemotaxis and random migration of these cells when zymosan-activated serum was used as the chemoattractant. When biochemical parameters were examined, it was demonstrated that, on a per-cell but not total-protein basis, alveolar macrophages from burned animals had elevated levels of RNA, total protein beta-glucuronidase, acid phosphatase, and 5'-nucleotidase. These results raise the possibility that the increased pneumonitis in burned individuals may be due to more complex macrophage dysfunctions than impaired microbicidal activity, as was once thought. Alternatively, the biochemical and functional changes observed may be a reflection of a new population of macrophages appearing in the lungs after thermal injury.

5'-Nucleotidase↗

PubMed1981

Corynebacterium parvum treatment of P388 tumor-bearing mice. I. Lysosomal enzyme levels in adherent peritoneal cells and peritoneal lavage fluid.

BDF1 mice treated with Corynebacterium parvum (C. parvum) 2 days before an implant of 106 P388 leukemic cells had up to an 110% increase in survival time above control; Bacillus Calmette-Guérin (BCG) treatment was ineffective. Acid phosphatase and beta-glucuronidase were measured in adherent peritoneal lavage cells and beta-glucuronidase in peritoneal lavage fluid form mice treated with C. parvum or BCG 2 days before the implant of P388 cells. In the presence of the tumor, adherent peritoneal cells from C. parvum-treated animals had a 250-300% increased specific lysosomal enzyme activity above control values (cells form animals receiving tumor implant alone). Peak enzyme activity which occurred on day 3 was not present in adherent cells from BCG-treated tumor-bearing animals or the control animals. The beta-glucuronidase activity in peritoneal lavage fluid was elevated by the tumor cells, BCG, or C. parvum. Peak levels occurred on day 5 regardless of the treatment with an additive effect present on day 5 in animals receiving the combination of tumor with C. parvum. The evidence indicated the development of a different pattern of enhanced lysosomal enzyme activity if the immunopotentiator protected against the P388 tumor vs one that did not. Protection was associated with an increase in lysosomal enzyme activity in adherent cells with no increase in lavage fluid in the presence of tumor cells. Changes in cellular enzyme activity may prove to be diagnostic for antitumor activity by an immunostimulant.

Acid Phosphatase↗

PubMed1981

Corynebacterium parvum treatment of P388 tumor-bearing mice. II. Lysosomal enzyme levels associated with P388 tumor cells.

The number of tumor cells recovered form the peritoneal cavity of mice administered Corynebacterium parvum (C. parvum), Bacillus Calmette-Guérin (BCG) or saline 2 days before tumor implant was assessed on days 1, 2, 3, 5 and 7 following the intraperitoneal (ip) administration of 10(6) P388 leukemic cells. C. parvum-treated mice manifested a significant decrease in the number of tumor cells recovered from the peritoneal cavity on days 3-7, while BCG-treated mice had tumor cell yields comparable to saline control values. Lysosomal enzyme activity (acid phosphatase and beta-glucuronidase) in the nonadherent lavage cell population, which comprised tumor cells and host cells obtained form tumor-bearing animals, closely reflected the changes observed in tumor cell numbers and was initially assumed to be associated with tumor cells. When lysosomal enzyme activity was expressed as a function of the number of tumor cells or cellular protein, an enhanced activity following C. parvum treatment but not following BCG treatment was demonstrated. Enzyme activity associated with tumor cells was maximal 2 days prior to the profound depression in tumor cell maximal 2 days prior to the profound depression in tumor cell yield and may be associated with tumor cell killing. It is concluded that a correlation may exist between lysosomal enzyme activity, tumor cell numbers and the protective effect of the immunostimulant C. parvum. Whether the correlation is direct or indirect remains to be resolved.

Acid Phosphatase↗

PubMed1980

Optimal conditions for antitumor activity of C. parvum against the ascites form of sarcoma 180.

Single and multiple doses of Corynebacterium parvum (C. parvum) ranging from 0.1--60 mg/kg were tested for antitumor activity against 10(6) sarcoma 180 cells in male CD1 mice. Determinations were made of the optimal dose and time of treatment needed to produce maximum suppression of the tumor using both median survival time and percent survival to day 90 as endpoints. A dose of 1 mg/kg given 3 days before sarcoma 180 transplant produced complete protection (100% survival). All other treatment regimens produced less of an effect. Single doses of 1, 10 and 60 mg/kg had significant antitumor activity when administered either on day 3, 2, or 1 before tumor implant, 0.1 mg/kg protected only when given on day 3. All single doses given 5 or 8 days before and anytime after tumor were ineffective. Multiple doses were only of advantage over single doses when treatments were after tumor cell inoculation. In vitro cytotoxicity studies demonstrated that both 1 and 60 mg/kg enhanced tumor cell killing by cells isolated from the peritoneal cavity, with the 1 mg/kg dose producing a greater effect. It was concluded that dose and time of administration of C. parvum, in relation to tumor implant, were important in determining optimal antitumor activity against sarcoma 180.

Animals↗

PubMed1980

Dose-dependent macrophage stimulation by Corynebacterium parvum.

Corynebacterium parvum (C. parvum) administered at a dose of either 0.1, 1 or 10 mg/kg intraperitoneally (ip) to BDF1 mice was evaluated for its influence on peritoneal exudate cell differentials, numbers, respiration, phagocytic activity and capacity and intracellular microbicidal activity. The ip administration of 1 mg/kg of C. parvum resulted in a 2-3 fold increase in the yield of peritoneal exudate cells 1-5 days after injection; 0.1 mg/kg was ineffective, while 10 mg/kg of C. parvum manifested an increased cell yield on days 1 and 5 following injection. No alterations in cell differentials were noted at any dose level. A trend toward a dose-related alteration in the respiratory burst, phagocytic activity and capacity was demonstrated. The most dramatic alteration observed was a profound increase in intracellular microbicidal activity in macrophages obtained from mice administered 1 mg/kg of C. parvum. The higher dose of C. parvum was suppressive. It was concluded that a relationship between macrophage microbicidal activity and tumor cell killing exists because the 1 mg/kg, which elicited maximal macrophage microbicidal activity, also induced the greatest increase in protection against two unrelated tumor models as previously reported.

Animals↗

PubMed1976