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Biomedical subjects

T M Saba

Publications and source records attributed to T M Saba.

At least 127 records · Page 7Linked to original sources
PubMed1979

A radial immunodiffusion method for the measurement of rat fibrinogen and fibrin degradation products.

The present report describes a technique for the production of monospecific rabbit antiserum to rat fibrinogen and its use in a quantitative radial immunodiffusion assay for measurement of rat fibrinogen and fibrin degradation products. It is a suitable technique for measurement of these parameters in small samples which can be repeatedly obtained from animals the size of rats.

Animals↗
PubMed1979

Immunoreactive serum opsonic alpha 2 sb glycoprotein as a noninvasive index of RES systemic defense after trauma.

Reticuloendothelial system (RES) depression has been correlated with diminished resistance to trauma, shock, and sepsis in man and animals. Previous studies have related the depression of RES hepatic Kupffer cell phagocytic function after trauma to diminished bioassayable opsonic activity. The present study determined if the loss of biological activity and RES alteration correlated with immunoreactive serum opsonic alpha 2 SB glycoprotein levels after trauma. Serum opsonic activity was measured by liver slice bioassay, and immunoreactive opsonic protein was measured by rocket electroimmunoassay. RE function was determined by colloid clearance over a 24-hour post-trauma period. Anesthetized rats (250-300 gm) subjected to sublethal or severe (greater than LD50) whole-body NCD trauma were the shock models investigated. Immunoreactive levels in 63 rats prior to injury were 518 +/- 24 microgram/ml. Neither biological nor immunoreactive levels were altered over 24 hours in anesthetized sham-traumatized controls. Temporal alteration in the initial decrease and recovery pattern of biologically active and immunoreactive opsonic protein levels significantly correlated following both sublethal and severe injury. Moreover, the patterns of immunoreactive levels of the opsonic protein correlated with the functional phagocytic activity of the RES as determined by vascular clearance of a test dose of blood-borne radiolabeled particulates. This glycoprotein falls after trauma, and the magnitude and duration of the decline increases with severity of injury. Immunoreactive opsonic alpha 2 SB glycoprotein appears to be an accurate measurement of circulating opsonic activity and RE Kupffer cell function after trauma, especially with respect to clearance. Thus, immunoreactive opsonic protein warrants clinical consideration as a noninvasive measure of reticuloendothelial systemic defense in patients after trauma and burn.

Animals↗
PubMed1979

Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

Animals↗
PubMed1979

Cardiovascular hemodynamics after opsonic alpha-2-surface binding glycoprotein therapy in injured patients.

Depression of reticuloendothelial (RE) phagocytic function has been clearly documented following trauma and operation. This phagocytic failure is mediated in part by depletion of an opsonic glycoprotein. Depletion of this opsonic protein may result in prolonged blood retention of potentially harmful particulates that may interfere with the microcirculation and may possibly result in altered organ function. Isolation and identification of this opsonic protein has led to the finding of the identity between opsonic glycoprotein and cold insoluble globulin (CIg) or so-called plasma fibronectin. Since CIg is concentrated in cryoprecipitate, this blood component was used as a readily available source of opsonic protein for replacement studies. Nine patients were studied following a 1-hour infusion of cryoprecipitate obtained from 10 units of plasma and suspended in a volume of 250 ml. Both the pulmonary shunt fraction and the fraction of dead space ventilation decreased significantly (P = 0.02) after cryoprecipitate administration. Limb blood flow (P = 0.001), limb oxygen consumption (P = 0.001), and reactive hyperemia of the limb (P = 0.05) increased significantly following cryoprecipitate infusion. Cardiac output, total oxygen consumption did not change consistently. The data demonstrate that the infusion of cryoprecipitate resulted in improved pulmonary and microcirculatory function--possibly due to opsonic glycoprotein replacement.

Cardiac Output↗
PubMed1978

Cryoprecipitate reversal of opsonic alpha2-surface binding glycoprotein deficiency in septic surgical and trauma patients.

Human opsonic alpha2-surface binding glyoprotein (alphs2SB-glycoprotein), a molecule having immunologic identity with an amino acid composition similar to cold-insoluble globulin, is concentrated in a cryoprecipitate of plasma. Septic surgical and trauma patients manifesting opsonic alpha2SB-glycoprotein deficiency and associated reticuloendothelial system dysfunction were treated by intravenous infusion of cryoprecipitate. This therapy restored circulating bioreactive and immunoreactive opsonin and improved their septicemia, pulmonary insufficiency, and duration of recovery. Cryoprecipitate infusion may offer a new approach to the treatment of septic injured patients in preventing multiple organ failure; measurement of immuno-reactive serum opsonic alpha2SB-glycoprotein may provide a noninvasive index of reticuloendothelial system function and patient status during servere sepsis that follows trauma.

Cryoglobulins↗
PubMed1978

Biochemical and immunological characterization of human opsonic alpha2SB glycoprotein: its identity with cold-insoluble globulin.

The relationship between human cold-insoluble globulin (CIg, plasma fibronectin) and the human serum opsonic alpha2SB glycoprotein was investigated using immunochemical and biochemical techniques. The two proteins appeared to have identical molecular weights by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 3.3% gels; have identical migration in the native state on 2.7 to 27% gradient polyacrylamide gels; and have a similar amino acid composition within the accuracy of analysis. Human serum demonstrates antigenic identity when diffused against monospecific antisera to both proteins confirming the presence of common antigenic sites on both molecules. Purified human serum opsonic alpha2SB glycoprotein and purified CIg also demonstrate antigenic identity when diffused against monospecific antiserum to either of the isolated proteins. Antiserum to both proteins also inhibits in vitro hepatic Kupffer cell phagocytic uptake of test particles. These results suggest the idenity of these two proteins and reveal a major physiological function for human plasma CIg. Thus, CIg may be important in the regulation of hepatic reticuloendothelial phagocytic activity and nonspecific systemic host defense. This process of systemic host defense has been shown to be depressed in patients following trauma, major surgery, burn injury, and during neoplastic disease, and, in part, mediated by a deficiency or depletion of the alpha2SB glycoprotein.

Amino Acids↗
PubMed1978

Prevention of liver reticuloendothelial systemic host defense failure after surgery by intravenous opsonic glycoprotein therapy.

Depression of the reticuloendothelial system (RES) was observed in rats following operative trauma consisting of laparotomy and jejunal enterotomy. This RES depression was manifested as a significant impairment in the phagocytic clearance of intravenously injected blood-borne test colloid mediated by a decline in hepatic Kupffer cell phagocytosis. Reticuloendothelial systemic host defense depression was correlated with a significant decline in bioassayable and immunoreactive opsonic alpha(2)SB glycoprotein concentration over a 1-3 hr postoperative period with rebound elevation in opsonic activity by 24 hr postsurgery. Intravenous administration of purified opsonic alpha(2)SB glycoprotein at the end of the operation prevented postoperative opsonic deficiency and restored normal hepatic RES phagocytic function. These studies coupled with previous observations in patients following surgery or after severe multiple trauma suggest that reticuloendothelial depression during and after operation mediated by opsonic deficiency may lead to a precarious imbalance between systemic host defense and the dissemination of blood-borne foreign and effete particulate matter such as injured platelets, fibrin microaggregates and immune complexes. Immunoreactive serum opsonic alpha(2)SB glycoprotein determinations may serve as a valuable index of hepatic RE clearance capacity and opsonin therapy may potentially be a selective means to augment systemic host defense.

Animals↗
PubMed1978

Opsonic alpha2 surface binding glycoprotein therapy during sepsis.

A pronounced depletion of an opsonic protein for hepatic reticuloendothelial (RE) phagocytosis has been demonstrated in critically ill trauma patients. This opsonic alpha(2) surface binding (SB) glycoprotein has immunologic identity and a similar amino acid composition to cold insoluble globulin (CIg). Since CIg can be concentrated in cryoprecipitate, it was utilized as a readily available source of opsonic alpha(2)SB glycoprotein for replacement therapy after injury with documented hypoopsonemia. Six septic patients (2 multiple trauma, 2 thermal burn, and 2 intra-abdominal abscess) were studied to test whether cryoprecipitate infusion would restore this humoral component. Pre- and posttherapy opsonin levels were determined by bioassay and electroimmunoassay. In all patients, severe opsonin depletion was reversed following cryoprecipitate infusion. All patients had a rapid improvement in febrile state, normalization of leukocyte levels, and improvement in pulmonary function as evidenced by decreasing requirements for end expiratory pressure at lowered levels of inspired oxygen. One patient was studied more extensively and demonstrated an increase in cardiac output, limb blood flow, total body and limb oxygen delivery, total body and limb oxygen consumption and a progressive decrease in pulmonary shunt fraction. Thus, opsonic alpha(2)SB glycoprotein deficiency can be reversed by cryoprecipitate infusion in critically ill septic injured patients. Replacement of this humoral factor may be an important therapeutic modality in prevention of multiple organ failure, but it should be administered only after documentation of hypoopsonemia in traumatized patients.

Adult↗
PubMed1978

Low-grade intravascular coagulation and reticuloendothelial function.

The present study evaluated the influence of experimentally produced intravascular coagulation on reticuloendothelial (RE) stability. Intravascular coagulation was initiated by the intraperitoneal injection of bovine thrombin (500 U/100 g body wt) into male rats. RE function was evaluated by the vascular clearance of an 131I-labeled RE test colloid. Thrombin injection resulted in a transient (0.5-2 h) (P less than .05) depression of the phagocytic index (K) with maximal depression at 1 h postthrombin challenge. The phagocytic index was unaltered after injection of saline or heat-inactivated thrombin. Vascular clearance depression was primarily due to a 37% decrease (P less than .001) in hepatic Kupffer cell colloid clearance and was associated with increments in lung (82%) and marrow (100%) colloid localization with no splenic alterations. While intravascular coagulation was associated with decreased hepatic blood flow at 30 min and 120 min, sinusoidal flow was normal during maximum RE impairment at 60 min. The in vivo clearance depression was not reflected as an intrinsic Kupffer cellular deficit when evaluated in an in vitro system. The results indicate a transient RE dysfunction during intravascular coagulation, the mechanism of which remains to be elucidated.

Animals↗
PubMed1978

Platelet removal from the circulation by the liver and spleen.

Previous studies on the clearance of intravenously administered platelets have focused primarily on the long-term survival of platelets rather than the mechanisms responsible for the rapid removal of altered platelets from the blood. In the present study the short-term blood clearance and organ localization of circulating labeled platelets were evaluated in rats during particle induced reticuloendothelial (RE) blockage and after intravenous injection of increasing platelet loads in normal rats. Platelet disappearance conformed to a two-compartment exponential clearance with quantifiable rapid (K1) and slow (K2) rate constants. As platelet load increased, the rapid rate constant decreased. This clearance alteration was associated with a decrease in the percent of the injected platelet load localized in the liver and an increase in lung localization. During RE blockade, a decrease was observed in the clearance rates of both the rapid and slow compartments. Such clearance alterations were associated with decreased hepatic platelet localization and increased pulmonary and splenic platelet localization. Thus, the hepatic reticuloendothelial system may represent a rapid cellular clearance system for altered platelets. When this cellular system is impaired or overloaded, the consequences are decreased hepatic and increased extrahepatic platelet localization.

Animals↗
PubMed1978

Cardiac output and regional blood flow following trauma.

The changes in cardiac output (Q), regional blood blow (Qr) and regional vascular resistance, and arterial pressure were studied in rats subjected to moderate (LD0) or severe (LD50) traumatic shock. Q and Qr were determined using microspheres at 15, 60 and 180 min posttrauma. Arterial pressure decreased in both groups at 15 min and recovered by 3 hr after sublethal (LD0) trauma, while arterial pressure did not return to control levels after LD50 trauma. Q decreased in both groups at 15 min and returned to control only in the LD0 trauma group by 3 hr. Cerebral, coronary, and hepatic arterial flows and resistances were maintained in both groups. Renal, intestinal, and splenic flows decreased and resistances increased in both groups by 15 min and returned to control levels by 3 hr only in the LD0 trauma group. Total hepatic and hepatic portal flows decreased at 60 min and returned to control levels at 3 hr after LD0 trauma, while there was significant depression in these parameters 3 hr after LD50 trauma. Therefore, sublethal and severe trauma resulted in early redistribution of flow favoring the coronary, cerebral, and hepatic arterial beds. However, renal, intestinal, splenic, and portal flows remained depressed only in severely traumatized rats, suggesting that continued hypoperfusion is a factor in the multiple organ failure and death following severe traumatic injury.

Animals↗