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Biomedical subjects

T M Saba

Publications and source records attributed to T M Saba.

At least 145 records · Page 8Linked to original sources
PubMed1977

Inhibition of phagocytosis and glucose metabolism of alveolar macrophages during pulmonary tumour growth.

Alveolar macrophage (AM) phagocytic activity and glucose metabolism were evaluated during lung tumour growth in adult rats challenged i.v. with 10(5) viable Walker 256 tumour cells. Phagocytosis was estimated by the in vitro uptake of (14)C-labelled Pseudomonas aeruginosa and glucose oxidation was evaluated by (14)CO(2) production from 1-(14)C-glucose. AM were harvested by lung lavage from rats prior to and at 7 and 21 days following i.v. tumour-cell challenge. Macroscopic lung tumour nodules were not observed by 7 days after tumour challenge. However, 3 weeks after tumour challenge, tumour nodules were clearly identifiable on the surfaces of the lungs. One week after the i.v. tumour challenge a marked increase in the number of AM was evident. The in vitro phagocytosis of (14)C-labelled Pseudomonas aeruginosa was unaltered at that time, but became progressively depressed thereafter. Three weeks after tumour challenge, this decrease in phagocytic activity was evident when cells were incubated in normal serum, and was furtheri ntensified by serum obtained from tumour-bearing animals. Glucose oxidation by AM in either the resting condition or during bacterial phagocytosis was clearly decreased at both 1 and 3 weeks following i.v. tumour challenge. These findings indicate that the growth of pulmonary metastases is associated with a depression of alveolar macrophage bacterial phagocytic capacity, perturbations in serum opsonic activity and distinct alterations in macrophage energy metabolism. The metabolic dysfunction may impair pulmonary macrophage host defences against lung tumour growth.

Animals↗
PubMed1977

Dynamics of insulin secretion and resistance after burns.

Alteration in the insulin regulation of carbohydrate metabolism following 20% surface burn injury in the rat was biphasic. At 4 hr after burn there was fasting hyperglycemia (92 +/- 6 (SE) mg/100 ml above controls) and a pronounced intolerance to 1 gm glucose/kg IV. Fasting serum insulin did not differ from controls and failed to rise appreciably following glucose administration. Two to four days after burn, the ability to cope with exogenous glucose was near normal or normal and the insulin response to standard glucose load was 41-69% higher than in the controls, indicating the presence of insulin resistance. This pattern was not altered by feeding the burned and control rats with glucose intragastrically, thus eliminating lower postburn food intake as the causal factor of exaggerated insulin response to IV glucose. Diaphragms from burned rats showed the same increase in glucose uptake in response to 0.1 U insulin/ml in vitro as those of controls, suggesting that the insulin resistance in vivo is not due to a decrease in the capacity of muscle to bind and respond to insulin.

Animals↗
PubMed1977

Electroimmunoassay of alpha-2-opsonic protein during reticuloendothelial blockade.

Physiological regulation of reticuloendothelial (RE) phagocytic activity by a plasma opsonic factor has been documented. In the recent study, serum levels of this alpha-2-opsonic protein in rats during colloid-induced RE blockade were measured utilizing an electroimmunoassay (Rocket immunoelectrophoresis) with monospecific antiserum to the purified alpha-2-glycoprotein. RE blockade was produced by the intravenous injection of the gelatinized "RE-test-lipid emulsion" at a dose of 50 mg/100 g body wt. The opsonic activity of serum at various intervals during colloid-induced RE blockade as measured by tissue slice bioassay manifested a high correlation (r = 0.98) with the serum opsonic protein concentration as measured by the electroimmunoassay. During RE blockade (30 min), there was a rapid depletion of the opsonic alpha-2-glycoprotein to 20% of the initial preinjection levels. Serum concentration of this glycoprotein remained low for at least 2-3 h after which time its concentration progressively increased with approximation of normal values by 6 h postblockade. Opsonic protein concentration at 24 h postinjection were significantly (P less than 0.05) elevated above controls. Thus, colloid-induced RE blockade is associated with the removal of this glycoprotein from the serum and recovery from RE blockade is accompanied by a restoration of opsonin levels. The electroimmunoassay can provide a sensitive technique to monitor this humoral factor known to exert a physiological control on the RE system.

Alpha-Globulins↗
PubMed1977

Reticuloendothelial phagocytic response to bacterial challenge after traumatic shock.

Resistance to intravenous (IV) and intraperitoneal (IP) bacterial challenge during periods of reticuloendothelial (RE) depression following trauma as well as the influence of bacteremia on RE phagocytosis were studied. The experimental shock model utilized was the anesthetized (2 mg/100 g sodium pentobarbital) male rat subjected to nonlethal Noble-Collip drum trauma. During post-traumatic RE depression (60 min after injury) rats were challenged IV or IP with Escherichia coli (1.02 X 10(10)). The clearance half-time of the bacterial load injected intravenously in controls was 1.23 +/- 0.10 min. In contrast, the half-time was 3.62 +/- 0.69 min after sublethal trauma (p less than 0.005) and associated with prolonged blood bacterial retention. Pulmonary localization of E. coli administered either IV or IP was elevated in traumatized rats. Comparison of routes of bacterial challenge with respect to blood levels of viable bacteria suggested lower host bacterial resistance to the IP injection as opposed to the IV route of administration. Production of experimental bacteremia in normal rats resulted in a 39% depression (p less than 0.01) of RE test colloid clearance rate accompanied by a 49% increase (p less than 0.01) in pulmonary colloid localization. The data suggest that depressed systemic RE clearance capacity following trauma may decrease systemic resistance to septicemia, and that severe bacteremia may further undermine the functional state of the reticuloendothelial system.

Animals↗
PubMed1976

Decreased resistance to intravenous tumour-cell challenge during reticuloendothelial depression following surgery.

The influence of surgical stress on resistance to i.v. challenge with Walker 256 tumour cells was investigated in rats, with respect to the functional state of the reticuloendothelial system (RES). Phagocytic activity of the RES was evaluated by colloid (gelatinized [131I] "RE test lipid emulsion") clearance, and opsonin levels were determined by bioassay. Reticuloendothelial clearance capacity was significantly (P less than 0-05) depressed 60 min following surgery (coeliotomy plus jejunal enterotomy) as quantified by both humoral and cellular parameters of RE function. Phagocytic depression was primarily due to impaired hepatic Kupffer cell function and related to a deficiency in the phagocytic supporting capacity of plasma, also referred to as opsonic or recognition factor (RF) capacity. During the postoperative period of RES colloid clearance depression, pulmonary localization of the blood-borne test particulate matter increased. Rats challenged with 51Cr-labelled viable tumour cells at a dose of 1-0 X 106 i.v., either prior to or during the postoperative period of RE depression, manifested a significant (P less than 0-05) increment in pulmonary localization of the viable tumour cells, and a decrease (P less than 0-05) in hepatic clearance. Evaluation of survival patterns demonstrated a significant (P less than 0-01) decrease in host resistance to i.v. tumour cell challenge (2 X 103 cells) during the postoperative period of RE depression and hypo-opsonaemia. Sham-anaesthetized control animals survived 17-9 +/- 0-8 days, while animals challenged during the period of RE depression survived 7-9 +/- 0-4 days. An increased incidence of respiratory distress and nasal discharge was observed in the animals with impaired survival. Thus, surgical manipulation may transiently compromise RES systemic host defence and may be reflected in an increment in the pulmonary localization of blood-borne tumour cells. The relationship of this altered pattern of tumour cell distribution to the impaired survival remains to be determined, and warrants investigations.

Animals↗
PubMed1976

Deficits in reticuloendothelial humoral control mechanisms in patients after trauma.

Plasma opsonic activity as expressed by an alpha-2-globulin which stimulates hepatic Kupffer cell phagocytosis, and thus modulates RES clearance, was determined in patients at varying intervals following whole-body trauma. Plasma opsonic activity decreased markedly following trauma in both nonsurviving (NS) and surviving (S) trauma patients as compared to an age- and sex-matched group of healthy volunteers. The initial post-traumatic hypoopsonemia (0-72 hr) was more severe (p less than 0.01) in nonsurviving patients than surviving patients. Survivors following trauma manifested restoration of opsonin levels with a definite transient rebound hyperopsonemia during the recovery phase (11-30 days); nonsurviving patients exhibited persistent systemic alpha-2-globulin opsonic deficiency. On the basis of previous animal and human studies, the presently observed humoral deficits following trauma in patients could contribute to impairment of reticuloendothelial Kupffer cell clearance of blood-borne particulate matter such as fibrin, damaged platelets, and other altered autologous tissue. The importance of post-trauma RES dysfunction to survival following severe injury warrants further investigation and clinical consideration.

Adolescent↗
PubMed1976

Humoral deficiency and reticuloendothelial depression after traumatic shock.

Circulating opsonin levels and reticuloendothelial (RE) phagocytic activity were investigated in anesthetized rats subjected to Noble-Collip drum (NCD) trauma. Reticuloendothelial function was assessed by colloid clearance kinetics and circulating opsonin levels by in vitro tissue slice bioassay. After sublethal shock, both hepatic RE phagocytosis and plasma opsonic activity were significantly (P less than 0.001) depressed in the 0.5- to 6-h posttrauma period. Pulmonary and bone marrow localization of the blood-borne test microparticles significantly (P less than 0.05) increased during hepatic RES depression. Hepatic RE cells from animals during the interval of posttraumatic in vivo phagocytic depression exhibited normal phagocytosis when incubated in normal pretrauma plasma and decreased phagocytic activity when incubated in posttrauma plasma. After sublethal shock, restoration or opsonin levels by 24 h after shock resulted in hepatic RE recovery. Plasma opsonin levels declined in direct relationship to the degree of trauma. Progressive hepatic RE failure was correlated with the progressive decline in circulating plasma opsonic activity. The findings indicate that opsonic depletion may be involved in the etiology of hepatic reticuloendothelial depression after traumatic shock.

Animals↗
PubMed1976

Reference sample method for cardiac output and regional blood flow determinations in the rat.

The reference sample method was used for simultaneous determinations of cardiac output and regional blood flows in conscious rats. Microspheres (15 +/- 5 mum in diam) labeled with strontium-85 were injected into the left ventricle and known volumes of reference sample were withdrawn from peripheral arteries. The calculated cardiac output measurements agreed with the previously reported values in rats. The percent distribution of the cardiac output to the brain, intestinal bed, and lungs were different from the reported values obtained in the rats using larger spheres. These differences may be related to the use of smaller spheres and to differences in the preparation. The absolute regional flows to various organs expressed in terms of milliliters per minute per gram tissue weight were also determined. The results indicate that the reference sample method can be applied to smaller mammals for determinations of regional flows and cardiac output.

Animals↗
PubMed1976

Correlation of plasma lysosomal enzyme levels with hepatic reticuloendothelial function after trauma.

Plasma lysosomal enzyme levels and hepatic phagocytosis were determined following Noble-Collip drum trauma in the rat. Circulating cathepsin and acid phosphatase activity increased after sublethal trauma (300 rev), reaching maximal levels at 1-3 hr and returning to pretrauma levels at 24 hr after trauma. Hepatic phagocytosis was decreased maximally at 1 hr and recovered to control levels at 24 hr after sublethal trauma. Increasing trauma intensity (100-500 rev) resulted in a progressive failure in hepatic Kupffer cell phagocytosis and a progressive increase in plasma lysosomal enzyme levels when tested at 60-min post-trauma. A significant inverse correlation was found between the plasma lysosomal enzyme levels and Kupffer cell phagocytosis after trauma. The functional significance of the relationship between these two parameters and its importance in shock survival remain to be determined.

Acid Phosphatase↗