Neutralizing antibody spectrum determines the antigenic profiles of emerging mutants of visna virus.

The visna viruses are antigenically related nononcogenic retroviruses of sheep. The original strain was isolated from the brain of a paralyzed sheep in Iceland during the 1940s. The prototype strains has been passed serially in sheep and has undergone progressive antigenic change. Previous reports have shown that such antigenic changes in visna virus can be reproduced in infected cell cultures treated with neutralizing antibody. We now show that the antigenic profiles of the emerging mutants directly reflect the nature of the selecting antibody. Mutants with minor antigenic changes were selected by "early" sera which had a limited neutralization range. Mutants with greater antigenic changes were selected by "late" sera with a wide neutralization range. Mutants selected by early sera emerged rapidly and consistently in cultures, and these were antigenically very similar to one another. Mutants rarely emerged in cultures treated with late sera, but these viruses showed major antigenic changes. The data suggest that the evolution of antigenic mutants of visna virus progresses by a series of minor mutations which accumulate under the selective pressure of antibody.     

Fast neutron radiotherapy for locally advanced prostate cancer: results of an RTOG randomized study

Between June 1977 and April 1983, the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized study investigating fast neutron radiation therapy in the treatment of patients with locally advanced (Stage C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation therapy or fast neutron irradiation used in a mixed-beam treatment schedule (neutron/photon). A total of 91 analyzable patients were entered in the study; 78 of them were treated without major protocol deviations. The two treatment groups were balanced in regard to all major prognostic variables. Actuarial curves for "overall" survival, "determinantal" survival and local/regional control are presented both for the entire group of 91 patients and the 78 patients treated within protocol guidelines. The overall local/regional tumor recurrence rate is 7% for the mixed-beam treated group of patients and is 22% for the photon (X ray) treated group of patients. The difference is statistically significant at the p = 0.05 level. For the entire group of 91 evaluable patients, the 5-year "overall" survival rate is 62% for the mixed-beam-treated group and 35% for the photon-treated group. This difference is also statistically significant (p less than 0.05). However, this statistical significance is lost when the smaller number of patients treated strictly within protocol guidelines is considered. The significance is regained (p less than 0.02) when one looks at "determinantal" survival, which uses active cancer at time of death as the failure endpoint. This study demonstrates that a regional treatment modality, in this case mixed-beam irradiation, can influence both local/regional tumor control and survival in patients with locally-advanced adenocarcinoma of the prostate gland.     

Recency-Weighted Statistical Modeling Approach to Attribute Illnesses Caused by 4 Pathogens to Food Sources Using Outbreak Data,United States

Foodborne illness source attribution is foundational to a risk-based food safety system. We describe a method for attributing US foodborne illnesses caused by nontyphoidal Salmonella enterica, Escherichia coli O157, Listeria monocytogenes, and Campylobacter to 17 food categories using statistical modeling of outbreak data. This method adjusts for epidemiologic factors associated with outbreak size, down-weights older outbreaks, and estimates credibility intervals. On the basis of 952 reported outbreaks and 32,802 illnesses during 1998–2012, we attribute 77% of foodborne Salmonella illnesses to 7 food categories (seeded vegetables, eggs, chicken, other produce, pork, beef, and fruits), 82% of E. coli O157 illnesses to beef and vegetable row crops, 81% of L. monocytogenes illnesses to fruits and dairy, and 74% of Campylobacter illnesses to dairy and chicken. However, because Campylobacter outbreaks probably overrepresent dairy as a source of nonoutbreak campylobacteriosis, we caution against using these Campylobacter attribution estimates without further adjustment.     

Management of unruptured incidentally found intracranial saccular aneurysms

Neurosurgical Review - Unruptured intracranial saccular aneurysms occur in 3–5% of the general population. As the use of diagnostic medical imaging has steadily increased over the past few...     

Recommendations for collection of laboratory specimens associated with outbreaks of gastroenteritis

Recent discoveries have implicated a number of "new" (i.e., previously unrecognized) infectious agents as important causes of outbreaks of gastroenteritis. Unfortunately, the ability to detect these agents in an outbreak can be limited by two factors: 1) the lack of appropriate assays-many of which are still in developmental stages and are not readily available to clinical laboratories, and 2) inadequately or improperly collected specimens. At CDC, many newly developed assays are being used for research and for outbreak investigations. The information in this report is especially intended for public health agencies that collaborate with CDC in investigating outbreaks of gastroenteritis. The report provides an update on guidelines and recommendations for the proper collection of specimens to be sent to CDC, gives general background information concerning some recently discovered pathogens, lists some of the tests available at CDC, and provides a list of CDC contacts. The guidelines and the general information provided on causes of outbreaks of gastroenteritis can be also used by public health workers for investigations when specific testing is available and appropriate.     

The cell cycle and induction of apoptosis in a hamster fibrosarcoma cell line treated with anti-cancer drugs: Its importance to solid tumour chemotherapy*

The induction of apoptosis by anticancer drugs and its relationship to stages of the cell cycle was studied in cells derived from a solid tumour; a highly malignant hamster fibrosarcoma (Met B). Asynchronously proliferating cells were treated with a wide variety of agents such as actinomycin-D, 1--D-arabinofuranosyl cytosine, camptothecin, cisplatin, cyclophosphamide, daunorubicin, 5-flurouracil, 6-mercaptopurine, hydroxyurea, ionomycin, methotrexate and vincristine. With the exception of cyclophosphamide and hydroxyurea, a 36 h exposure to these drugs resulted in inhibition of cell growth and apart from cyclophosphamide, hydroxyurea, 6-mercaptopurine and cisplatin the induction of apoptosis. Studies using a decreased concentration of drug and exp osure time (12 h) followed by examination of cells using flow cytometry indicated that most drugs were capable of affecting cell cycle progression without induction of apoptosis. However when cells were synchronised at G₀/G₁, S and G₂/M phases and then exposed to these decreased concentrations of drug apart from 6MP an HU, apoptosis was observed and for the majority of drugs it took place in the same phase in which progression through the cell cycle was blocked by the drug. Cells synchronised in G₀/G₁ phase were more susceptible to methotrexate, whereas S-phase cells were more susceptible to camptothecin and 5-flurouracil and G₂/M phase cells more susceptible to actinomycin D, 1--D-arabinofuranosyl cytosine, daunorubicin and cisplatin. In contrast, vincristine blocked cells in G₂/M phase but exerted its apoptotic effect in S-phase cells, ionomycin had no effect on the cell cycle, but G₂/M cells appeared to be more susceptible to the effect of this drug. These data indicate that entry into apoptosis by this fibrosarcoma may occur at any point in the cell cycle. They also demonstrate a correlation between the action of some anticancer drugs on the cell cycle and the subsequent induction of apoptosis which may be useful in chemotherapeutic design.     

The proximo-distal spread of axonal degeneration in the dorsal columns of the rat

Summary The pivotal event in Wallerian degeneration is the breakdown of the axon. Establishing the pathophysiology of axonal degeneration has implications for the understanding of the pathogenesis of other types of nerve degenerations. A key aspect of the pathophysiology is the spatiotemporal pattern of spread after transection, an issue that has remained controversial. We have studied the progression of axonal degeneration in the dorsal columns of the rat following L₄L₅L₆ dorsal radiculotomy. Axonal degeneration proceeds in a proximo-distal fashion, beginning near the site of transection and spreading up the dorsal columns at a net rate of about 3 mmh^–1. In addition, there was early degeneration of the preterminal axons in the gracile nuclei. This pattern suggests that the clearing of axonally transported materials from the distal stump by continued anterograde transport may underlie axonal breakdown after transection.