Korean hemorrhagic fever: propagation of the etiologic agent in a cell line of human origin.

The etiologic agent of Korean hemorrhagic fever has been propagated in a human cultured cell line derived from a carcinoma of the lung. The cells, described as type II, alveolar epithelial, support replication of the agent and successive passages. Antigen of the Korean hemorrhagic fever agent is readily detected in infected cells by means of direct or indirect fluorescent antibody techniques. Previous attempts to propagate this agent in vitro had been unsuccessful.

In vitro assessment of the effects of granulocyte-macrophage colony-stimulating factor on primary human tumors and derived lines.

One hundred eighty-nine human tumor specimens were tested in a human tumor cloning assay to determine their growth response to human recombinant granulocyte-macrophage colony-stimulating factor. Of these samples 48 were evaluable for response. Growth stimulation to greater than 150% of controls was noted in 1 of 12 lung cancers (8%) and 1 of 14 breast cancers (7%) but in no other instances for an overall rate of 2 of 48 (4.2%). A dose-response effect was not seen with each of the two stimulated samples responding only at the two lowest concentrations tested. In addition, 7 cell lines derived from human tumors were tested using a metabolic CO2 production assay without evidence of growth stimulation. Samples of normal bone marrow displayed the usual dose-dependent stimulation whether grown in agar or assayed metabolically. We conclude that human recombinant granulocyte-macrophage colony-stimulating factor has minimal effect on the growth of the solid tumors tested and that clinical trials to reduce chemotherapy-associated myelo-suppression may proceed without undue concern for enhancement of tumor growth.

Observations on natural and laboratory infection of rodents with the etiologic agent of Korean hemorrhagic fever.

Studies were conducted to define the natural host range of the Korean hemorrhagic fever (KHF) agent in South Korea, and to identify colonized rodents susceptible to this infection. Eight species of field rodents were captured in areas of Korea endemic for KHF and their tissues were examined by immunofluorescence for the presence of KHF antigen. One hundred and fourteen of 817 Apodemus agrarius coreae captured between 1974 and 1978 had one or more positive organs. No positive organ was found in 239 rodents of the other seven species examined. Two hundred and thirty-eight specimens of Apodemus agrarius jejuensis captured on Jeju Island, an area thought to be free of disease, were also negative. Attempted laboratory infection of nine species of rodents captured in the field but maintained in the laboratory was successful only in the two subspecies of Apodemus. The 46 specimens of A. a. jejunesis tested in this manner were all uniformly susceptible to infection as determined by immunofluorescence. Serial sacrifice of experimentally infected A. a. jejuensis revealed viremia of short duration terminating on day 10 postinfection. In contrast, other tissues of this animal, including lung, kidney, liver and parotid gland were positive on day 10 and remained so through the 100-day observation period. When 12 species of colonized laboratory rodents were inoculated with KHF agent five were found to develop KHF antibody by indirect immunofluorescence and two, Calomys callosus and Apodemus agrarious ningpoensis, developed detectable KHF antigen in their tissues.

Human coagulation factor FVIIa (recombinant) in the management of limb-threatening bleeds unresponsive to alternative therapies: results from the NovoSeven emergency-use programme in patients with severe haemophilia or with acquired inhibitors.

This open-label, emergency-use study evaluated the efficacy and safety of activated human coagulation factor VIIa (recombinant) (rFVIIa) (NovoSeven; Novo Nordisk Pharmaceuticals, Inc., New Jersey, USA) in treating limb-threatening joint or muscle bleeds in 17 patients with haemophilia A or B and six patients with acquired inhibitors to factor VIII or factor IX. All patients had previously failed on one or more alternative therapies. rFVIIa administration was effective or partially effective in controlling joint or muscle bleeds in 34 out of 35 (97%) bleeding episodes; in 23 patients, 14 of 17 (82%) muscle bleeds and 16 of 18 (89%) joint bleeds were effectively controlled. These findings suggest that rFVIIa is an effective and well-tolerated therapeutic option in the management of joint or muscle haemorrhage in patients with haemophilia and in patients with acquired inhibitors.

Structural polypeptides of Hazara virus.

Four structural polypeptides of Hazara virus, an agent closely related to the Crimean-Congo haemorrhagic fever (C-CHF) viruses, were resolved by SDS-polyacrylamide gel electrophoresis. Three glycoproteins were identified (mol. wt. 84,000, 45,000 and 30,000) and were found to be associated with the virion envelope. A fourth polypeptide (mol. wt. 52,000) was non-glycosylated and associated with the nucleocapsid. The structural proteins of Hazara virus differ markedly from those reported for other bunyaviruses.