Biomedical subjects
Publications and source records attributed to S Louie.
Benign lesions may simulate bronchogenic carcinoma by virtue of radiologic appearance or false-positive cytologic studies. A lung opacity initially suspected to be malignant was, on review, considered to be a loculated effusion. Needle biopsy yielded cells which appeared malignant. The resected lesion was a benign infarct.
A single-chain 55,000-mol wt form of urokinase (UK), similar to that previously isolated from urine, was purified from a transformed kidney cell culture medium and characterized; and its fibrinolytic properties were evaluated. The preparation immunoprecipitated with UK antiserum, had a low intrinsic amidolytic activity that was 0.1% of its active derivative, and resisted diisopropyl fluorophosphate treatment and inactivation by plasma inhibitors. The single-chain UK was therefore designated pro-UK. In the presence of plasmin and during clot lysis, activation by conversion to two-chain, 55,000-mol wt UK (TC-UK) was demonstrated. This did not occur during blood clotting nor on incubation with purified thrombin. Clot lysis in plasma consistently occurred in 2-5 h with 50-100 IU per ml of pro-UK, whereas comparable lysis was inconsistently achieved by 500-1,000 IU of UK. Pro-UK, in sharp contrast to UK, caused no fibrinogen degradation at fibrinolytic concentrations. In the absence of a clot, pro-UK in plasma was stable for more than 2 d. When a clot was added after incubation (37 degrees C) for 50 h, activation to full lytic activity took place. The findings in vivo were comparable but the rapid clearance of pro-UK required that it be given by a constant infusion despite its plasma stability. In rabbits, a UK-resistant species, pro-UK was significantly (P less than 0.001) more efficacious than TC-UK but neither induced significant fibrinogen degradation. In dogs, a more sensitive species, the high specificity of thrombolysis by pro-UK contrasted with the defibrinogenation and uncontrollable bleeding that accompanied thrombolysis by UK. It was concluded that clot lysis by pro-UK is more effective and specific than UK. The advantage of pro-UK is in the limitation of its activation to the site of a clot. This can be explained by an activation mechanism that is dependent, under physiological conditions, on fibrin-stabilized plasmin.
The antithrombotic effect of aspirin (ASA) and dipyridamole (DIP) was evaluated in rabbits in which platelet thromboxane A2 (TXA2) and arterial prostacyclin (PGI2) were measured. An intracarotid cannula thrombosis model previously shown to be sensitive to antiplatelet agents was used. Prostaglandins were determined by radioimmunoassays for thromboxane B2 (TXB2) and 6-keto-prostaglandin PGF1 alpha, the stable metabolites of TXA2 and PGI2. In the aspirin-treated animals, reduction in thrombosis was seen only in rabbits which received a low-dose (1-2 mg/kg), and was related to a selective suppression of platelet TXA2. In contrast, higher doses of ASA (10 or 100 mg/kg), which suppressed both TXA2 and PGI2, were not associated with thrombus inhibition. DIP alone had a lesser antithrombotic effect which was augmented by low-dose ASA but not by high-dose ASA. It is concluded that 1) the antithrombotic effect of ASA in this animal model is dependent on selective TXA2 suppression; 2) ASA has no antithrombotic properties beyond its inhibition of prostaglandin synthesis by platelets; 3) selective suppression of TXA2 in vivo can be achieved in rabbits by a single dose of ASA but only over a narrow dose-range; 4) DIP may have an antithrombotic effect additive to that of low-dose ASA; 5) measurement of serum TXB2 may be used to determine the minimal ASA dose necessary to suppress TXA2 and therefore be most likely to spare PGI2.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Forty tissue samples, primarily of skin and bone, were obtained from 29 patients undergoing excision of decubitus ulcers after intravenous injection of 600 mg of clindamycin. Antibiotic concentrations exceeded 2.5 mug/g in 80% of the samples. In 50% of the instances, tissue levels were greater than those simultaneously present in the serum.
Explore the source record for details and available documents.
Some human marrows in culture release particles with oncornavirus-like properties. This study was designed to examine the immunological properties of similar particles in human marrow culture supernates. Leukemic and nonleukemic marrows were cultured for 5-7 days in the presence of [14C]uridine and [3H]leucine or [3H]glucosamine. Labeled supernatant components banding in sucrose gradient densities of 1.20-1.24 g/ml were used as antigen in a double antibody immunoprecipitation assay. The assay was validated by end point titrations and competition with unlabeled antigen; purified myeloma proteins were used as negative controls. Cross-reactivity with mammalian oncornaviruses, as judged by competitive inhibition of precipitation by these viruses, was slight and at the border of the sensitivity of the method. Precipitated antigens analyzed by SDS polyacrylamide gel electrophoresis contained three distinct polypeptides of about 70,000, 45,000 and 30,000 mol wt; these comigrated with the gp 70, pg 45, and p 30 of a murine leukemia virus. Similar polypeptides were obtained from both leukemic and nonleukemic marrow culture supernates. As determined by the radioimmunoprecipitation assay, 32 of 45 leukemic sera (71%), 36 of 45 normal sera (80%), 15 of 19 sera from family contacts of leukemic patients (79%), 14 of 21 cord blood specimens (67%), and 21 of 23 sera (91%) from patients with systemic lupus erythematosus had detectable antibody activity.
A combined virologic and immunologic study was done in mice that were either naturally or deliberately infected with C-type RNA viruses. In about 60% of B10. A mice, natural infection was accompanied by detectable anti-VEA antibodies in the serum. The absence of such antibodies was a reliable indicator of the absence of virus in B10 mice. Deliberately infected young adult B10 mice failed to eliminate the virus completely, despite high titers of anti-VEA antibodies. B10 mice exposed to B tropic viruses at birth made anti-VEA antibodies but failed to eliminate the virus. By contrast, some NIH Swiss mice exposed to N-tropic virus at birth made anti-VEA antibodies and eliminated the virus.
The incidence of infectious murine leukemia virus (MuLV) in congenic-resistant C57BL mice was studied. No constant relationship between the incidence of MuLV and the H-2 complex was apparent. Two lines, B10 and B10.A, were examined in detail because the incidence of MuLV in B10 was low and the virus appeared relatively late in life, whereas B10.A animals had a relatively high incidence of infection by MuLV early in life. Further studies of B10.A mice revealed an almost universal concordance between the virologic status of the mother and her offspring. This was particularly evident when (B10 times B10.A)F1 animals were compared with (B10.A times B10)F1 mice: Although genetically identical, the incidence of MuLV in the latter was high, whereas in the former it was low. Transmission of MuLV by milk was proved by foster-nursing experiments; when the infants of MuLV-positive B10.A mothers were suckled on MuLV-negative B10.A mothers, they were free of MuLV. Milk-borne infection may account for the natural dissemination of MuLV among some inbred lines of mice.
A modified XC assay for murine leukemia virus (MuLV) employing splenocytes taken directly from the animal is described. This modification can be more than 1000 times more sensitive than XC plaque assays employing tissue extracts. This technique should lend itself readily to the quantitation of infectious MuLV in defined populations of lymphoid cells.
Explore the source record for details and available documents.
Explore the source record for details and available documents.