Iris cavernous hemangioma associated with multiple cavernous hemangiomas in the kidney, brain, and skin.

Purpose: To document the relationship of iris cavernous hemangiomas with multiorgan hemangiomas in a child.

Methods: A 7-year-old girl with kidney hemangiomas, brain hemangiomas, and skin hemangiomas developed blurred vision and darkening of the right iris. She had undergone 6 previous brain surgeries and multiple revisions of a ventriculoperitoneal shunt for hydrocephalus beginning at age 3 months.

Viral safety and clearance evaluation--implications for process change and comparability.

A key component in the development of safe cell-based biologicals is the incorporation of procedures to ensure virological safety using a three-pronged approach--raw material testing, including testing of the cell banks; incorporation of virus clearance steps in the production process; and lot-by-lot virus testing of culture harvests. During the development of a biological, changes are made to improve product quality, purity, yield, and consistency and to meet other production requirements. It is important to evaluate process changes in view of virus safety.

Sudden painless visual loss.

Common signs and symptoms of temporal arteritis include headache, scalp tenderness, jaw claudication, anemia, and an elevated sedimentation rate (ESR). Severe complications can include blindness, retinal artery occlusion, and optic neuropathy. While temporal arteritis may be suggested by patient history, other causes that can mimic its presentation must be considered, especially when visual loss occurs in the setting of a normal funduscopic exam.

Quantitative competitive reverse transcription-PCR as a method to evaluate retrovirus removal during chromatography procedures.

Chinese hamster ovary cells used for pharmaceutical protein production express non-infectious retrovirus-like particles. To assure the safety of pharmaceutical proteins, validation of the ability of manufacturing process to clear retrovirus-like particles is required for product registration. Xenotropic murine leukemia virus (X-MuLV) is often used as a model virus for validation studies.

Failure of cast immobilization for thumb ulnar collateral ligament avulsion fractures.

To determine if small avulsion fractures of the thumb ulnar collateral ligament (UCL) with minimal (< or = 2.0 mm) displacement can successfully be treated by cast immobilization, the authors reviewed 9 patients with minimally displaced fractures initially treated by casting. Despite immobilization within an average of 2 days of the initial injury (range, 0-6 days), a minimum of 6 weeks of immobilization in a cast, and adequate rehabilitation, all 9 patients had persistent thumb pain, especially with activities requiring strong pinch.

Genetic stability and recombinant product consistency.

A committee of U.S. industry scientists from the Pharmaceutical Manufacturers Association has reviewed the recent suggestions of Galibert and Center for Biologics Evaluation and Research (CBER) regarding assurances of product consistency by cloning and sequencing efforts.

Recent studies on retrovirus-like particles in Chinese hamster ovary cells.

Highly concentrated (4000-7000-fold) culture fluids from CHO cells were analysed for the presence of retrovirus-like activity. Concentrates containing reverse transcriptase activity were detected and further purified by sucrose density gradient centrifugation. Particles banding at 1.

Endogenous origin of defective retroviruslike particles from a recombinant Chinese hamster ovary cell line.

The presence of budding C-type and intracytoplasmic A-type particles in Chinese hamster ovary (CHO) cells is well documented. However, extensive screening has failed to detect any evidence of infectivity. Continuous-flow ultracentrifugation has been used to concentrate extracellular particles from culture fluid of a recombinant CHO cell subclone for molecular characterization.

Defective endogenous retrovirus-like sequences and particles of Chinese hamster ovary cells.

The presence of budding C-type and intracytoplasmic A-type particles in Chinese hamster ovary (CHO) cells is well documented. However, extensive screening has failed to detect any evidence of infectivity. To investigate the origin and expression of these particles, retrovirus-like sequences which are actively transcribed in CHO cells have been cloned and characterized.

Thirteen-week toxicity study of d-alpha-tocopheryl acetate (vitamin E) in Fischer 344 rats.

A 13-wk study was conducted by administering d-alpha-tocopheryl acetate (vitamin E) in corn oil by gavage to groups of ten male and ten female Fischer 344 rats at doses of 0, 125, 500 or 2000 mg/kg body weight daily for 13 wk. The dose of corn oil given was 3.5 ml/kg.

Naturally occurring humoral immunity to endogenous xenotropic and amphotropic type-C virus in the mouse.

Natural humoral cytotoxic antibodies from 13- and 18-month-old BALB/c mice showed a virus-specific complement-dependent activity against target cells productively infected with xenotropic, amphotropic or ecotropic type-C viruses. The cytotoxic activity was lowest against ecotropic virus-shedding cells. Serum obtained from mice less than 12 months old had no such reactivity.

Naturally occurring lymphocyte-mediated immunity to endogenous type-C virus in the mouse. Blocking of the lymphocyte reactivity with antisera to the virus.

The natural immune response in mice to their endogenous type-C viruses involves a complex interaction between cellular and humoral immune mechanisms. The virus-specific immune reactivities are a function of age and appear only subsequent to endogenous virus expression. Cellular immune activity was found to reside in a population of lymphocytes that were characterized as natural killer cells based on their absence of theta surface antigens or immunoglobulin or complement receptors.

Cytoplasmic DNA synthesis in rhinovirus type 14-inoculated KB cells.

Rhinovirus type 14 (RV14) incuced a transient statistically significant stimulation in synthesis of DNA which appeared between 0 and 3 h post-inoculation in the cytoplasm of high density monolayer cultures of KB cells. Newly synthesized DNA was measured by incorporation of [3H] thymidine into acid-insoluble DNAase-sensitive material and the cytoplasmic location established by cell fractionation and electron microscope radioautographic methods. A minimum of 10 plaque-forming units per cell of RV14 was required to stimulate DNA synthesis which did not occur above 34.

Susceptibility of murine transfer factor to dimerized ribonuclease A.

Dialyzable transfer factor was prepared from the spleens of CF1 mice actively sensitized with killed Coccidioides immitis antigen. The transfer factor was administered to normal mice either intraperitoneally or into the hind footpads. The recipient mice were tested for reactivity to the coccidioides antigen and to Candida albicans antigen by means of the footpad swelling test.

Transfer of delayed hypersensitivity in mice to microbial antigens with dialyzable transfer factor.

Dialyzable Lawrence-type transfer factor was prepared from the spleen cells of CF1 mice inoculated with Coccidioides immitis- and Candida albicans-killed vaccines and with live Mycobacterium tuberculosis vaccine (BCG). These preparations were shown to transfer antigen-specific cell-mediated immunity to naive mice, as measured by the delayed skin test and footpad-swelling methods. Reactivity could be demonstrated when the test antigens were given 24 h after the transfer factor, but not when they were given simultaneously.

A continuous line of Rous sarcoma virus-transformed chick embryo cells.

A continuous line of Rous sarcoma virus (RSV)-transformed chick embryo cells was established. The cells, designated RTAZ-1, which constitute the only known line of continuously growing RSV-transformed cells of chick embryo origin, grow rapidly, display uniform morphology, and perpetually release large amounts of RSV (Rous-associated virus, type 1). RTAZ-1 cells display a heteroploid chromosome complement with 92-94 chromosomes characteristic of chicken cells.

Particles resembling oncornaviruses. Spontaneous release from cultured meningioma cells.

A cell culture from thoracic cord meningioma tissue obtained at surgery was maintained for several passages in cell culture. These cells spontaneously released particles with an RNA of high-molecular weight (90S to 95S) and a density similar to that of type C oncornaviruses. The implications of these results and similar findings by others are discussed.

Altered sensitivity of Rous sarcoma virus transformed cells to inhibition of RNA synthesis by alpha-amanitin.

Chick embryo cells transformed by Rous sarcoma virus (RSV) continue to synthesize 40--50 percent of control amounts of RNA following 12--24 hour exposure to 2 microng/ml of the toxin whereas normal chick embryo cells similarly treated synthesize less than 5 percent of control amounts of RNA. Analysis of cells treated with alpha-amanitin, or the resistant forms I and III polymerase, do not increase in infected cells over the levels found in uninfected control cells during the first 24 hours following infection indicating that increase in polymerase levels in infected cells does not account for the observed resistance. No significant difference was detected in the sensitivity to alpha-amanitin in the form II polymerase isolated from normal and transformed cells; The greater sensitivity of normal cells to alpha-amanitin can be reduced by growing the cells at low cell density but the resistance of RSV transformed cells is not significantly altered by changes in cell density.

Delayed hypersensitivity to fungal antigens in mice. II. Characterization of the active component in immunogenic RNA extracts.

In a mouse model, cell-mediated immunity to Coccidioides immitis, as assayed by the delayed hypersensitivity skin test, was transferred with whole immunogenic RNA extract and its greater than 33S and 6S-13S sedimentation fractions. Both fractions were cleaved by RNase, but the products retained their transfer activity. The greater than 33S fraction of immunogenic RNA extract was inactivated by pronase, whereas the 6S-13S fraction was resistant to the proteolytic enzyme; however, after RNase treatment the latter fraction was sensitive to pronase.

Delayed hypersensitivity to fungal antigens in mice. II. Molecular classes in immunogenic RNA extracts that transfer delayed hypersensitivity.

The transfer of delayed hypersensitivity to Coccidioides immitis and Candida albicans antigens with immunogenic RNA extracts was studied in a mouse model. Sensitivity was measured by skin tests and footpad swelling responses. Immunogenic RNA converted normal spleen cells in vitro so that they produced antigen-specific delayed hypersensitivity in mice that were given injections of the cells.