Structure-function relationship of 3-phosphoglycerate analogues with platelet aggregation and thromboxane A2 formation.

We have studied the effects of 2,3-diphosphoglycerate (2,3-DPG), 3-phosphoglycerate (3-PG), 3-phosphoglyceraldehyde (3-PGA), 2-phosphoglycerate (2-PG) and beta-glycerol phosphate (beta-GP) on platelet aggregation and on thromboxane B2 (TXB2) formation. The results show that 2,3-DPG, 3-PG, and 3-PGA inhibited platelet aggregation and TXB2 formation induced by norepinephrine, ADP, epinephrine, and collagen; but they also induced platelet aggregation and TXB2 formation in the presence of subthreshold concentrations of Na arachidonate. 2-PG and beta-GP were inactive. The results also show that there is a structure-function relationship between 2,3-DPG, 3-PG, and 3-PGA with platelet aggregation phenomena and prostaglandin synthesis.

Immunodetection of neuron-specific enolase and keratin in cytological preparations as an aid in the differential diagnosis of lung cancer.

The results of neuron-specific enolase (NSE) and keratin immunodetection in cytological specimens of sputum secured from 41 patients with lung cancer are presented. All 19 cases of small-cell carcinoma showed intense immunoreactivity for NSE. No such immunoreactivity was found in 21 of 22 cases of non-small-cell carcinoma. The single positive result was from a case of large-cell undifferentiated carcinoma. All 10 cases of squamous-cell carcinoma showed immunoreactivity for keratin. The 19 cases of small-cell carcinoma showed no such reactivity. Our findings indicate that immunostaining for NSE and keratin is a valuable aid when a definite diagnosis of small-cell carcinoma of the lung can not be made on the basis of conventional cytologic features.

The combined effects of 2,3-DPG and Na-arachidonate on platelet aggregation and on TXA2 formation.

We have investigated the effects of 2,3-DPG on platelet aggregation in the presence of suboptimal concentrations of Na-Arachidonate by using the two cuvette transfer experiments of Hamberg, Svensson and Samuelsson (3). The results show that 2,3-DPG enhanced or induced platelet aggregation in the presence of suboptimal concentrations of Na-Arachidonate. Imidazole, a TXA2 synthetase inhibitor, and Lasix, when added inhibited 2,3-DPG effects on platelet aggregation, suggesting that 2,3-DPG may act either on cyclooxygenase or on TXA2 synthetase of prostaglandin synthesis. A specific RIA assay showed that 2,3-DPG when added to suboptimal concentrations of Na-Arachidonate enhanced the formation of TXB2, a stable metabolite of TXA2. We have concluded that during intravascular hemolysis 2,3-DPG release may be a key component in preventing and/or inducing thrombosis.

Detection of benign or malignant origin of ascites with combined indirect immunoperoxidase assays of carcinoembryonic antigen and lysozyme.

The indirect immunoperoxidase method was used to study the presence of the intracellular carcinoembryonic antigen (CEA) and lysozyme (LZ) in alcohol-fixed cytologic smears of peritoneal fluids from 2 patients with chronic active hepatitis, 31 patients with liver cirrhosis and 7 patients with malignant liver disease. In the two patients with hepatitis, LZ was positive in both CEA was positive in one and negative in the other. Of the 31 patients with liver cirrhosis, 21 (67.5%) were LZ positive, 27 (87%) were CEA negative and only 4 (13%) were CEA positive. Of the seven patients with malignant disease, six were CEA positive and six were LZ negative. It is of interest that 23 of 24 (96%) LZ-positive results and 28 of 29 (97%) CEA-negative results corresponded to negative cytologic diagnoses for malignancy. Cytologic diagnosis of "reactive mesothelial cells" seemed to correlate better (71%) with CEA-negative and LZ-positive results. The data suggest that the investigation of CEA and LZ in the cells of peritoneal fluids appears to have promise as an adjunct to cytology in differentiating benign from malignant origins of the fluid.

The cytologic application of carcinoembryonic antigen for the discrimination of malignant from benign serous effusions.

In an attempt to diminish false cytologic diagnosis in discriminating between benign and malignant effusions, the value of intracellular carcinoembryonic antigen (CEA) was estimated in cytologic smears of effusions using a modified immunoperoxidase technique. CEA serum level was estimated by radioimmunoassay technique. In this study we included a group of 42 patients, 23 with a malignant and 19 with a benign effusion. CEA in cells of effusions was positive and useful for confirming malignancy in 65% of malignant effusions. The percentage increased to 83% with the combination of the results of positive CEA in cells and serum. Cytology was positive for malignancy in 16 of the 23 (70%) malignant cases. CEA in cells of benign effusions was negative in 84% and cytology in 100%. It is concluded that intracellular CEA estimation, when combined with CEA estimation in serum, improves the discriminating range of cytology for differentiating malignant and benign effusions.

The role of HF cofactor in the Hageman factor-dependent fibrinolytic mechanism.

In 1969, Ogston et al. reported that the normal activation of fibrinolysis by surface contact requires, in addition to Hageman factor and plasminogen, a HF cofactor which is present in the euglobulin fraction and other factor(s) present in the supernatant. It has also been suggested that the glass-treated plasma is deficient in HF cofactor, In our laboratory the glass-treated plasma was found not to be deficient in HF or in a streptokinase-activated proactivator or in plasminogen. The glass-treated plasma was found deficient in prekallikrein in kininogen and in clotting factors XI, IX, VIII and V. The results presented indicate that HF cofactor activity is not different from that of kallikrein and that HF cofactor does not act as a plasminogen proactivator. Furthermore, the results indicate that the "other factors' present in the supernatant are not involved in contact-activated fibrinolysis.

Stimulation of human platelet aggregation by phospholipase-A and a saline "extract" of a polyurethane.

A saline extract of polyurethane (SPU) induces enzymatic conversion of arachidonic acid (either exogenous or released through the action of exogenous phospholipase-A) by activating a hitherto undiscovered labile enzyme, synthetase-alpha which is not blocked by aspirin. Addition of SPU, plus arachidonic acid or SPU plus phospholipase-A to platelet-rich plasma (PRP) triggers a biphasic platelet aggregation. Incubation of SPU with PRP results in activation and exhaustion of synthetase-alpha; this renders platelets refractory to the various aggregating agents.

2,3-diphosphoglycerate: a physiological inhibitor of platelet aggregation.

2,3-Diphosphoglycerate (2,3-DPG) may inhibit the platelet release reaction and the irreversible aggregation of human blood platelets induced by adenosine diphosphate, epinephrine, or norepinephrine. The effects of 2,3-DPG on platelet aggregation were more pronounced in cases with low hematocrit (less than 30 percent). Dipyridamole and vincaminor potentiated the antiaggregating effect of 2,3-DPG. Erythocytes (10-3 to 10-4 per microliter) exhibited a similar antiaggregating effect, especially when secured from anemic patients.