No abstract

We have used rocket immunoelectrophoresis and immunoblotting to detect myeloperoxidase in synovial fluid from patients with rheumatoid arthritis. This protein was enzymatically inactive but its identity as myeloperoxidase was confirmed by comparing its subunit structure with that of the purified enzyme. When neutrophils were stimulated to secrete myeloperoxidase in vitro, a polypeptide with an apparent molecular mass of 62 kDa was detected extracellularly by immunoblotting. Neutrophils isolated from synovial fluid showed a reduced level of this 62 kDa polypeptide but it was detected extracellularly in synovial fluid by immunoblotting. Thus, we conclude that neutrophils in synovial fluid from patients with rheumatoid arthritis have been activated in vivo to secrete myeloperoxidase and propose that the products of this enzyme system can contribute to the tissue damage associated with this disease.

No abstract

Treatment with adriamycin (ADM) and bleomycin (BLEO) alone and in combination has been evaluated in 56 patients with a variety of advanced stage gynecologic cancers. ADM has a high degree of antitumor activity against uterine sarcomas (leiomyosarcoma and stromal sarcoma) and some of the unusual ovarian cancers including ovarian teratoma. ADM was also active and gave clinically worthwhile responses against squamous cell carcinoma of the cervix and vagina. Occasional objective remissions were seen in patients with epithelial ovarian adenocarcinomas. The combination of ADM plus BLEO appeared to show no enhancement of the effect achieved by ADM alone. There were no objective responses in patients with squamous cell carcinoma of the cervix treated with BLEO alone. The usual toxic manifestations of ADM and BLEO were observed, and there appeared to be no potentiation of the toxicity of each agent when used in combination. It is concluded that ADM is a valuable chemotherapeutic agent for certain gynecologic cancers which are usually refractory to other chemotherapeutic agents. Further investigation of its use alone and in combination with other drugs is indicated.

Type II (inducible) nitric oxide synthase (NOS) may play an important role in pulmonary pathophysiology, yet it remains controversial whether human tissues are capable of expressing this protein. Therefore, a polyclonal antibody (8196) was raised against type II NOS from induced RAW 264.7 macrophages and used to investigate the expression of this enzyme in human lung tissue. Anti-type II NOS antibody did not cross-react with either neuronal (type I) or endothelial (type III) constitutive NOS, whereas a 130-kDa protein was detected in cytosol from induced macrophages or liver removed from lipopolysaccharide (25 mg/kg)-treated rats. Cells or tissues that lacked NOS activity did not express immunoreactive proteins. Similarly, in grossly normal human lung tissue, no immunoreactivity was detected with the anti-type II NOS antibody. In contrast, strong immunoreactivity was detected in alveolar macrophages present in lung tissue from a patient with bronchiectasis and acute bronchopneumonia. These data demonstrate that human alveolar macrophages are able to express type II NOS and support a role for this enzyme in pulmonary inflammatory pathophysiology.