Photo by Thea Goepfert

Divining the Centrosome’s Role in Cancer:

Pulled from the biomedical dustbin, a peripheral organelle finds center stage

Eugene Russo, The Scientist 18:19:18, 11 Oct 2004

MUTAGENS AND MITOSIS: Section cut through the mammary gland of a rat that had been treated with the carcinogen MNU. Centrosomes (green) are arranged at the base of each nucleus (red), and 45% of cells show amplified chromosomes.

Comments from journal article reviewers often surprise or frustrate. But the reviewer response that cell biologist William Brinkley received six years ago left him stunned.

Brinkley and his collaborator, Subrata Sen at the University of Texas M.D. Anderson Cancer Center, were looking to demonstrate that a protein found on centrosomes, the organizing centers for microtubules during mitosis, disrupted cell division and possibly triggered carcinogenesis. Reviewers praised the work, but declared it incomplete. Brinkley and his colleagues, they instructed, needed to experimentally demonstrate that the protein of interest, when inserted into a diploid cell and induced to produce in excess, actually generated more centrosomes and converted the cell to aneuploidy. Amazingly, the reviewer had unwittingly asked Brinkley to prove a theory first proposed by pioneering biologist Theodor Boveri 80 years earlier.

“It was just almost uncanny,” says Brinkley, dean of the graduate school of biomedical sciences at Baylor College of Medicine, and a long-time admirer of Boveri’s work.

Boveri had a rather simple model for carcinogenesis. What distinguishes cancer cells from normal cells, he wrote in 1914, is abnormal chromosome number (later called aneuploidy); the wrong combination of chromosomes stems from aberrant centrosome number. “All he had at his disposal, literally, was a microscope,” says Jeffrey Salisbury, a professor of molecular biology at the Mayo Clinic College of Medicine in Rochester, Minn. “This guy just sat down and looked.” Following Brinkley’s lead, several researchers have rediscovered Boveri’s work in recent years while elucidating centrosome-associated cell-cycle proteins with potentially key roles in carcinogenesis.

WDDTY reports:

It is tragic that it has taken 16 years to vindicate the controversial discoveries of Dr Jacques Benveniste – and in the very week that he has died.

Dr Benveniste scientifically proved the basis of homeopathy in a series of experiments with water, which were published in Nature in 1988. Thereafter the medical establishment pilloried him, research funding was taken away, and his very promising career in science was ended. Television magician James Randi visited Benveniste’s laboratories but, not surprisingly perhaps, was unable to verify his discovery.

But scientists … have finally proved his findings. Four independent laboratories, in Ireland, Italy, France and the Netherlands, have discovered that effects can occur below the level at which any molecule of the substance is present.

Histamine dilutions modulate basophil activation

P. Belon1, J. Cumps2, M. Ennis3 , P. F. Mannaioni4, M. Roberfroid5, J. Sainte-Laudy6 and F. A. C. Wiegant7

Inflammation Research 53:5:181-188, April 2004

(1) Boiron, 20 rue de la Libération, 69110 Sainte-Foy-Les-Lyon, France

(2) UCL 7369, 73 avenue Emmanuel Mounier, 1220 Brussels, Belgium

(3) Department of Clinical Biochemistry, Institute of Clinical Science, The Queens University of Belfast, Grosvenor Road, BT12 6BJ Belfast, United Kingdom

(4) Department of Pharmacology, Pieraccini 6, 50139 Florence, Italy

(5) Laboratoire de biotoxicologie, 73 avenue Emmanuel Mounier, 1220 Brussels, Belgium

(6) Laboratoire dImmunologie et dAllergologie, 5 boulevard Montparnasse, 75006 Paris, France (7) Department of Molecular Cell Biology, University of Utrecht, 3508 Utrecht, The Netherlands

Abstract Background: In order to demonstrate that high dilutions of histamine are able to inhibit basophil activation in a reproducible fashion, several techniques were used in different research laboratories.

Objective: The aim of the study was to investigate the action of histamine dilutions on basophil activation.

Methods: Basophil activation was assessed by alcian blue staining, measurement of histamine release and CD63 expression. Study 1 used a blinded multi-centre approach in 4 centres. Study 2, related to the confirmation of the multi-centre study by flow cytometry, was performed independently in 3 laboratories. Study 3 examined the histamine release (one laboratory) and the activity of H2 receptor antagonists and structural analogues (two laboratories).

Results:High dilutions of histamine (10–30–10–38 M) influence the activation of human basophils measured by alcian blue staining. The degree of inhibition depends on the initial level of anti-IgE induced stimulation, with the greatest inhibitory effects seen at lower levels of stimulation. This multicentre study was confirmed in the three laboratories by using flow cytometry and in one laboratory by histamine release. Inhibition of CD63 expression by histamine high dilutions was reversed by cimetidine (effect observed in two laboratories) and not by ranitidine (one laboratory). Histidine tested in parallel with histamine showed no activity on this model.

Conclusions: In 3 different types of experiment, it has been shown that high dilutions of histamine may indeed exert an effect on basophil activity. This activity observed by staining basophils with alcian blue was confirmed by flow cytometry. Inhibition by histamine was reversed by anti-H2 and was not observed with histidine these results being in favour of the specificity of this effect. We are however unable to explain our findings and are reporting them to encourage others to investigate this phenomenon.

Cancer Research has just published a paper on electromagnetic (EM) field effects on cancer cells. There are numerous papers in the biophysics journals using random frequencies to achieve effects reported by Prof. Lai at the Rife International Conference this weekend in Seattle. However, this is one of the first papers published in a leading cancer research journal.

It is amazing to me that researchers keep getting results without using the correct frequencies. If they knew what they were doing they would kill all the cancer cells in these experiments.

Disruption of cancer cell replication by alternating electric fields.

Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y.

Cancer Res. 2004 May 1;64(9):3288-95.

Low-intensity, intermediate-frequency (100-300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3-6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.

I find that some of the leading scientists in the U.S. are not aware of the fact that every thought generates a recognizable chemical reaction in the brain that can be seen on a brain scan. Furthermore these chemical reactions generate enzymes, proteins, and other forms of signaling in the body.

Elsewhere, I have already reported on recently studies showing that emotional tone directly impacts immune function. Here we seen that human cells can manufacture morphine. It is not surprising that placebo effects have been occassionally shown to be more powerful than morphine.

Human cells produce morphine

Results of biosynthesis studies may improve understanding of pain, immunity, and behavior

Charles Q Choi

The Scientist, September 21, 2004

Researchers in Germany have found solid evidence that human cells can generate morphine. Their findings, reported this week in PNAS, may help resolve years of debate.

“If this morphine [that] humans produce interacts with opiate receptors in the body, this could open up a whole new era for understanding the pharmacological modulation of pain, of immune response, and of behavior,” author Meinhart Zenk of Martin Luther University in Halle, Germany, told The Scientist.

George Stefano, director of the Old Westbury Neuroscience Institute in New York and a leading proponent of endogenous morphine’s debated existence, said the study, which he did not participate in, confirms nearly 30 years of theories. In 2003, his group cloned an opiate receptor from human tissues, mu3, that only reacts with morphine and is found in immune, vascular, and neural tissues.

Mediterranean Diet, Lifestyle Factors, and 10-Year Mortality in Elderly European Men and Women

The HALE Project

Kim T. B. Knoops, MSc; Lisette C. P. G. M. de Groot, PhD; Daan Kromhout, PhD; Anne-Elisabeth Perrin, MD, MSc; Olga Moreiras-Varela, PhD; Alessandro Menotti, MD, PhD; Wija A. van Staveren, PhD

JAMA. 2004;292:1433-1439.

ABSTRACT

Context: Dietary patterns and lifestyle factors are associated with mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer, but few studies have investigated these factors in combination.

Objective: To investigate the single and combined effect of Mediterranean diet, being physically active, moderate alcohol use, and nonsmoking on all-cause and cause-specific mortality in European elderly individuals.

Design, Setting, and Participants: The Healthy Ageing: a Longitudinal study in Europe (HALE) population, comprising individuals enrolled in the Survey in Europe on Nutrition and the Elderly: a Concerned Action (SENECA) and the Finland, Italy, the Netherlands, Elderly (FINE) studies, includes 1507 apparently healthy men and 832 women, aged 70 to 90 years in 11 European countries. This cohort study was conducted between 1988 and 2000.

Main Outcome Measures: Ten-year mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer.

Results: During follow-up, 935 participants died: 371 from cardiovascular diseases, 233 from cancer, and 145 from other causes; for 186, the cause of death was unknown. Adhering to a Mediterranean diet (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.68-0.88), moderate alcohol use (HR, 0.78; 95% CI, 0.67-0.91), physical activity (HR, 0.63; 95% CI, 0.55-0.72), and nonsmoking (HR, 0.65; 95% CI, 0.57-0.75) were associated with a lower risk of all-cause mortality (HRs controlled for age, sex, years of education, body mass index, study, and other factors). Similar results were observed for mortality from coronary heart disease, cardiovascular diseases, and cancer. The combination of 4 low risk factors lowered the all-cause mortality rate to 0.35 (95% CI, 0.28-0.44). In total, lack of adherence to this low-risk pattern was associated with a population attributable risk of 60% of all deaths, 64% of deaths from coronary heart disease, 61% from cardiovascular diseases, and 60% from cancer.

Conclusion: Among individuals aged 70 to 90 years, adherence to a Mediterranean diet and healthful lifestyle is associated with a more than 50% lower rate of all-causes and cause-specific mortality.

It is a good idea to regularly scan for viral infections. In combination with a suppressed immune system, a parasite, or restrictions on breathing, they can be deadly.

New Virus Suspected in Two SIDS Cases

Wed Sep 1, 6:33 PM ET

By MARILYNN MARCHIONE, AP Medical Writer

MILWAUKEE – A virus recently discovered in Japan is suspected in two “crib deaths” in Wisconsin, raising new questions about how many of these mysterious tragedies might be caused by germs.

The cases mark the first time the virus has been identified in the United States. Whether it killed the babies is not clear, but both were sick before they died and had signs of disease in their lungs.

Sudden infant death syndrome — also called “crib death” for the devastating way it is usually discovered — is a catch-all term for unexplained deaths in children less than a year old. About 2,200 occur each year in the United States, mostly involving babies between 2 and 4 months old.

Brain or breathing abnormalities, genetic mutations and birth defects are possible causes. The risk rises if babies live with smokers, are put to sleep on their stomachs, or are bundled in too many clothes or covers.

Infections also have long been implicated. However, many SIDS victims are not tested for viruses that might be the culprit.

The Wisconsin cases should prompt research into whether SIDS is often caused by the newly discovered type of virus, said Dr. Mark Pallansch, who identified it at the federal Centers for Disease Control and Prevention after a Milwaukee virologist detected it.

A question came up today on variations of resonant frequencies for an organ depending on tissue type and I searched my archives for a report I posted in October 2001. The frequencies below refer to a specific infection and strain of the shistosoma parasite.

24 Oct 2001

Recently, I had a minor toothache after a trip to Tampa and detected a parasite with frequencies: 353585, 273873, 111755, 37735. Treating with the F-SCAN quickly knocked out the toothache but I had stomach symptoms so treated it for two days without success. This provided a great opportunity to example this problem in some detail to find a treatment strategy to eliminate it quickly. Normally, any parasite can be eliminated with a two minute treatment at the right frequencies to the right organ(s). So the fact that symptoms were still there after two days indicated that the organism was hiding out where it could not be reached or the frequencies were not correct.

This parasite appeared to be Shistosoma mansoni which I first picked up in a delicious dinner of sea scallops on Martha’s Vineyard last August. As a result, I was quickly able to identify a reinfection in Tampa. Shistosoma (blood flukes) infect over 200 million people in Africa, Asia, and Latin America. It is second only to malaria as the greatest threat to human health in these regions. See http://idrinfo.idrc.ca/Archive/ReportsINTRA/pdfs/v7n2e/109595.pdf

“There are three major species of schistosoma (The disease is often called schistosomiasis.) that infest humans:Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum. The male schistosome is a flat worm about 1 cm long, the sides of its body inverted to form a groove in which the female is carried. After mating the pairs move to the veins of the bowel (in the case of S. mansoni and S. japonica) or the bladder (S. haematobium). The females periodically leave the males and deposit eggs in the small portal veins in these areas. Most eggs penetrate the walls of the veins: some become trapped in the tissues there, scarring and hardening it. Others work their way into the bladder and bowels and are eliminated. Eggs eliminated in the urine or feces must reach water to survive.

“Once in water, the eggs split and the larvae (known now as miracidia) penetrate the bodies of freshwater snails, which then become the intermediate hosts. Inside the flesh of the snail host the miracidia develop into a type of reproductive cyst. Some weeks later, depending on the species, these cysts produce numerous minute free-swimming larvae called cercariae. In this tadpole-like stage, the parasite swims vigourously upwards and drifts downwards in the water, searching for its principal host… humans.

“After contact with the human host, the cercariae penetrate the skin (shedding their tails in the process) and move through the lymphatic system to the arteries, through the heart and lungs, and eventually appear in the liver. The complete process is not yet understood. The larvae grow rapidly in the blood vessels of the liver, then migrate to the bowel or bladder. There the mature worms mate and begin laying eggs. Egg production usudlly begins about 40 days after penetration of the skin. The female can lay hundreds (and in the case of japonica, thousands) of eggs per day. Infection has been known to last as long as 28 years, although it is generally of much shorter duration.”

Since I had snails in Florida shortly before the toothache, I wondered if I picked it up in the wonderful French restaurant I ate in. I have previously found gourmet French restaurants to be a great source of parasite infections for study and analysis.

Using plate zapping with the F-SCAN by putting microscopic slides on top of the cylinder than comes with the F-SCAN, I found the parasite had infected the liver, lung, prostate, stomach, and thymus. I then proceeded to identify the frequencies in each organ, and found that an exact match within 10HZ was necessary to kill the parasite with less than two minutes of treatment at each frequency.

353673, 273889, 112666, 37686 tooth

353496, 273887, 112174, 37742 liver

353986, 273799, 112579, 37687 lung

353496, 273689, 112599, 37437 prostate

353678, 273887, 112698, 37659 stomach composite

353669, 273887, 112898, 37687 thymus

I have since puzzled over these numbers recalling Aubrey Scoon’s paper on the secret of the Rife effect:

“The significance of this becomes clearer when we realise that Rife’s resonance effect (if it exists) must be dependent on wavelength. But we also know from the above that the wavelength of any given frequency of radiation inside the body tissues must be different to the wavelength of the same radiation outside the body. And if this is true, then there is no way that any one frequency can resonate the same object equally both inside and outside the body tissues.”

And I would add that the frequency within specific tissues will be different. This is the entire basis of medical imaging techniques.

To dig a little deeper into this, I found the following frequencies were indicated by the F-SCAN software. This was after all symptoms were gone due to treatment with frequencies above.

Adult: 353020, 353440, 353500, 353570, 353790, 353800, 353810, 353860, 353940, 353950

Larva (late stage): 273020, 273030, 273870

Larva (early stage): 112030, 112040, 112150, 112190, 112210, 112220, 112490, 112510

Egg: 37030, 37040, 37080, 37400, 37700, 37910, 37960, 37980, 37990, 38000

Are these residual organisms in various tissue types? I have noticed this phenomenon often and assumed it was due to multiple strains. However, this infection seemed to start very localized and may be a single strain. The impedance may be different in various organs and cause different frequencies to be required to eliminate the pathogen.

Current strategies for dealing with cancer mainly involve killing cells and hoping enough healthy cells survive. The problem is that the healthy cells are often in various stages of being programmed into cancer cells by continued insults to the cellular environment and recurrence is problematic. Reprogramming the cells requires more sophisticated strategies. Initially, elimination of cancer associated pathogens is essential, while in the long term nutritional and lifestyle changes are mandatory.

At the most primary level, all molecular movement is electromagnetic in nature and manipulation of the electromagnetic environment of the cells can cause important effects.

Cracking the Cellular Code

MIT Technology Review

By Erika Jonietz, September 9, 2004

In the past few years, biologists have churned out the entire genetic sequence of dozens of organisms, including humans, dogs, mosquitoes, rats, and bacteria. But these strings of genes amount to the most basic molecular parts list, not much more helpful to deciphering how the genes combine to run a living cell than an array of microchips and wires would be for assembling a computer.

Researchers at MIT and at the MIT-affiliated Whitehead Institute for Biomedical Research have taken a major step toward understanding how those genes are organized to regulate cells. Refining a technique pioneered in geneticist Richard Young’s lab, the team has identified all of the controlling elements in the genome of baker’s yeast, a common laboratory microorganism.

“A parts list is nice, but in moving to an understanding of how a whole cell behaves, this is really the next step,” says Young, who headed the project with Whitehead fellow Ernest Fraenkel and MIT computer scientist David Gifford. “We’ve been able to identify an important part of the genome in a very precise way that is key to regulation of life.” Fraenkel and Gifford published their findings in the September 2 issue of the journal Nature.

Any cell, from yeast to human, uses multiple layers of control to coordinate which genes are switched on and off in response to stimuli such as temperature, nutrient availability, and outside chemical messengers. The central method of gene control, however, relies on proteins known as transcription factors. When these molecules attach to a region of DNA close to a particular gene, that gene is switched on; when the protein detaches, the gene shuts down. Mutations in transcription factors or in their binding sites on the genome are associated with many diseases, including hypertension, cancer, and diabetes.

(… modern horses represent the single surviving twig of a once luxurious, and now depleted, clade, and not the apex of a continually progressing trend). By the same argument, generalized to all of life, we understand the stability and continued domination of bacteria as the outstanding feature of life’s history, with the much vaunted progress of complexity towards mammalian elegance reinterpreted as a limited drift of a minor component of diversity into the only open space of complexity’s theoretical distribution… Hominid evolution must also be rethought as reduction of diversity to a single species of admittedly spectacular (but perhaps quite transient) current success. Stephen Jay Gould

Stephen Jay Gould (2002) The Structure of Evolutionary Theory. Harvard University Press.

Stephen Jay Gould’s magnum opus rewards serious study (and study you will to understand his ramblings). For electronic medicine, there is no more important field of study than the evolution of microorganisms, and understanding evolutionary theory is basic to gaining depth in the area.

Evolutionary theory is one of the few great ideas in the history of science, and the only idea where the work of the original proponent, Charles Darwin himself, is as relevant to evolutionary arguments today as the year in which he wrote the first edition of his work.

I recommend the book only to those who love the pain of intellectual discovery, the joy of insight, and the wrenching voyage of new understanding. You may or may not agree with Gould in the end and the journey will be as painful (although potentially enlightening) as a pilgrimage to Mt. Kailash in Tibet. You will need a dictionary and access to the internet to make sense of his terminology and concepts if you are not an expert in the field.

“The world’s most revered and eloquent interpreter of evolutionary ideas offers here a work of explanatory force unprecedented in our time–a landmark publication, both for its historical sweep and for its scientific vision. With characteristic attention to detail, Stephen Jay Gould first describes the content and discusses the history and origins of the three core commitments of classical Darwinism: that natural selection works on organisms, not genes or species; that it is almost exclusively the mechanism of adaptive evolutionary change; and that these changes are incremental, not drastic. Next, he examines the three critiques that currently challenge this classic Darwinian edifice: that selection operates on multiple levels, from the gene to the group; that evolution proceeds by a variety of mechanisms, not just natural selection; and that causes operating at broader scales, including catastrophes, have figured prominently in the course of evolution. Then, in a stunning tour de force that will likely stimulate discussion and debate for decades, Gould proposes his own system for integrating these classical commitments and contemporary critiques into a new structure of evolutionary thought. In 2001 the Library of Congress named Stephen Jay Gould one of America’s eighty-three Living Legends–people who embody the “quintessentially American ideal of individual creativity, conviction, dedication, and exuberance.” Each of these qualities finds full expression in this peerless work, the likes of which the scientific world has not seen–and may not see again–for well over a century. Stephen Jay Gould is the Alexander Agassiz Professor of Zoology at Harvard University and Vincent Astor Visiting Professor of Biology at New York University. A MacArthur Prize Fellow, he has received innumerable honors and awards and has written many books, including Ontogeny and Phylogeny and Time’s Arrow, Time’s Cycle (both from Harvard).”

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More Cancer Risk Seen in Full-Body CT Scans

By Thomas H. Maugh II and Daniel Costello, Los Angeles Times, 31 Aug 2004

Whole-body CT scans, long controversial because of doubts about their effectiveness in finding hidden disease, can significantly increase the recipient’s risk of developing cancer, according to a study released Monday.

The radiation from a single whole-body scan is equal to that from 100 mammograms and is similar to that received by survivors of the atomic bombings of Hiroshima and Nagasaki, Japan — about 1 1/2 miles from the explosions — according to radiation biologist David J. Brenner of Columbia University.

The radiation from one scan is enough to produce a tumor in every 1,200 people who undergo the procedure, reported Brenner and coauthor Carl D. Elliston of Columbia in the journal Radiology. For those who have annual scans, the risk goes as high as one tumor in every 50 people, they said.

Brenner, D. J. and C. D. Elliston (2004). “Estimated Radiation Risks Potentially Associated with Full-Body CT Screening.” Radiology 232(3): 735-738.

PURPOSE: To estimate the radiation-related cancer mortality risks associated with single or repeated full-body computed tomographic (CT) examinations by using standard radiation risk estimation methods.

MATERIALS AND METHODS: The estimated dose to the lung or stomach from a single full-body CT examination is 14-21 mGy, which corresponds to a dose region for which there is direct evidence of increased cancer mortality in atomic bomb survivors. Total doses for repeated examinations are correspondingly higher. The authors used estimated cancer risks in a U.S. population derived from atomic bomb-associated cancer mortality data, together with calculated organ doses from a full-body CT examination, to estimate the radiation risks associated with single and multiple full-body CT examinations.

RESULTS: A single full-body CT examination in a 45-year-old adult would result in an estimated lifetime attributable cancer mortality risk of around 0.08%, with the 95% credibility limits being a factor of 3.2 in either direction. A 45-year-old adult who plans to undergo annual full-body CT examinations up to age 75 (30 examinations) would accrue an overall estimated lifetime attributable risk of cancer mortality of about 1.9%, with the 95% credibility limits being a factor of 2 in either direction.

CONCLUSION: The authors provide estimates of lifetime cancer mortality risks from both single and annual full-body CT examinations. These risk estimates are needed to assess the utility of full-body CT examinations from both an individual and a public health perspective. (C) RSNA, 2004