RxPG News : Pathology

AApoAII amyloidosis demonstrated to be transmissible to offsprings

Mon, 01 May 2006 00:52:37 PST

( from http://www.rxpgnews.com ) Researchers have demonstrated spread of senile amyloidosis from affected mice to their nursing offspring. The paper by Korenaga et al., "Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis," appears in the March issue of The American Journal of Pathology and is highlighted on the cover of the Journal.

Dementia can result from several disease mechanisms, including amyloidosis. Amyloidosis occurs when cellular proteins that normally float freely in the body form organized, nonfunctional aggregates, or fibrils, that cause cellular damage. This injury can lead to such disorders as Alzheimer's disease and Creutzfeld-Jakob disease, depending on the protein involved and where the fibrils accumulate.

Genetics are known to be involved in these disorders, but researchers have also shown that injecting fibrils into susceptible mice accelerates disease onset. That led researchers guided by Dr. Xiaoying Fu to ask whether pups born to affected mothers also display accelerated disease.

Using a mouse strain that carries a mutation for senile amyloidosis, Dr. Fu's group injected female mice with amyloid fibrils, to accelerate their disease, and then allowed the mice to mate and produce offspring. The mouse pups born to these mothers exhibited elevated levels of amyloid fibrils that increased with age. These fibrils were first seen in the intestines, spreading later to liver, spleen and other organs.

Interestingly, when mice born to injected mothers were nursed by control mothers (no fibrils injected), only one of nine pups had amyloid fibrils at 6 months. However, pups born to control mothers but nursed by injected mothers had amyloidosis at levels similar to that of pups born/nursed by injected mothers. The presence of fibrils in the milk of injected mothers was confirmed by protein assay and electron microscopy, and spread via the milk was demonstrated by injecting affected milk into naïve mice (fibrils were found at 3 months).

These authors use traditional "infectivity" concepts to show that ingestion of fibrils by nursing mouse pups, and not by events occurring in utero, transmits amyloid fibrils to their offspring, thus accelerating amyloidosis. Such events have not been observed in human amyloidosis but have been suggested in sheep scrapie, a prion disease related to Creutzfeld-Jakob disease.

Prion diseases, such as scrapie and bovine spongiform encephalopathy (mad cow), are known to be transmissible, with spread among susceptible hosts demonstrated in the laboratory and in the real world. Non-prion amyloidosis, however, has not been shown to spread in such a way until now.

Though provocative, the implications for such laboratory findings in human disease, such as Alzheimer's disease, are not clear. The study does, however, suggest interesting new areas for study of amyloidosis.

Cell phone electromagnetic radiation does not activate the stress response in cells

Thu, 13 Oct 2005 15:10:38 PST

( from http://www.rxpgnews.com ) Weighing in on the debate about whether cell phones have adverse health effects, researchers at Washington University School of Medicine in St. Louis have found that the electromagnetic radiation produced by cell phones does not activate the stress response in mouse, hamster or human cells growing in cultures.

The stress response is a cellular protection mechanism set into motion by various adverse stimuli, including heat shock, heavy metals, and inflammation. High levels of the stress response in cells are thought to result in changes associated with malignancy.

"We performed highly sensitive, extremely well-controlled tests on living cells irradiated with energy like that from mobile phones, but at levels 5 to 10 times higher than those set for the devices by regulatory agencies," says Andrei Laszlo, Ph.D., associate professor of radiation oncology and a researcher at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. "We see no indication that factors involved in the stress response increase their activity as a result of such exposures."

Prior research into the effect of cell phones on the stress response has been fraught with contradictory results, which in part may be due to less-than-ideal experimental conditions. For example, in the past it has been difficult to prevent temperature changes caused by microwave exposure.

Because heating of tissues has been shown unlikely to be a component of the effect of cell phone radiation on biological systems, Laszlo and his group sought to reduce as far as possible any heating of the cells in culture during the study. Using sensitive equipment that continuously monitored and adjusted temperature, they were able to keep temperature variations to plus or minus 0.3 degrees centigrade.

The researchers tuned their room-sized irradiator to emit cell phone frequency microwaves for both FDMA (frequency domain multiple accessused for cell phone analog signals) and CDMA (code domain multiple accessused for digital signals) modulation at power outputs standard for mobile phones. The large size of the irradiator enabled them to expose a large number of living cells so that sufficient material could be collected for highly accurate measurements.

"We were able to combine very good physics with very good biology as a consequence of the expertise of our research team," Laszlo says.

To test whether the cell's stress response was activated by irradiation, the group looked for activation of a protein called heat shock factor (HSF). The activation of HSF is a necessary first step in the cascade of events that induce the stress response.

Under both short-term exposures (5-60 minutes) and long-term exposures (1-7 days), all tests on the cells in culture showed that HSF was not activated by microwave radiation of either type, indicating the stress response was not initiated.

"We've done extensive studies on the effect of cell phone radiation in our research group in the past as well," Laszlo says. "Dr. Joseph Roti Roti and his colleagues have examined the potential for DNA damage and cellular transformation, and the effect of microwave radiation on animals has been studied also. Now we've conducted this study of the molecular mechanisms of the stress response. In every case we've looked at, our group saw no biological effects of cell phone radiation that could cause cancer."

Researchers found strong associations between sarcoidosis and insecticide exposure

Thu, 16 Dec 2004 16:47:38 PST

( from http://www.rxpgnews.com ) In a large study involving 10 clinical research centers throughout the United States, researchers found strong positive associations between the disease sarcoidosis and occupational exposure to insecticides in both agricultural and industrial settings, as well as with occupational exposure to "moldy" and "musty" environments.

The investigators studied 706 newly diagnosed sarcoidosis patients, together with an equal number of age-race-, and sex-matched control subjects. They were trying to understand what environmental and occupational exposures were associated with the disease. (Although it has no known etiology, sarcoidosis is an illness in which abnormal clusters of inflammatory cells called granulomas form in many organs of the body, especially in the lungs. In those organs, inflammation can lead to scarring and cyst formation.) The authors noted that one of the strongest positive associations in the study was for occupational exposure to insecticides at any time before participation in the study, particularly in the 3 years preceding diagnosis.

They point out that agricultural workers encounter high levels of exposure to chemicals and aerosolized particulates, including grains, bedding materials, silicates, animal proteins, insect proteins, fungi, bacteria, mycotoxins, and endotoxins. They pointed out that exposure to tobacco smoke at any time in the past seemed to provide a strong negative association with sarcoidosis, a finding which they could not explain.