Electrophysiological findings in humans who are performing voluntary acts, indicate that the intention to act, follows brain activity rather than preceding it. This has implications for voluntary behavior and the doctrine of free will. This essay reviews the fields of human behavior, including medicine, in which this new thesis might have far-reaching significance.
This case study demonstrates that the normal human body frequency, which can be disturbed by electromagnetic influences of the environment, can be modulated by 0.9% sodium chloride solutions (physiological saline) and that occurrence of allergic reactions have subsequently been suppressed as a result of this modulation. The use of distilled water as control showed no effect on occurrence of allergic reactions. Further observations on the growth of various plants in a greenhouse exposed to various geomagnetic fields support the previous observations on humans. The neutralization of electromagnetic influences on humans using 0.9% sodium chloride solution or by enclosure of plants within a copper wire Faraday cage resulting in a normal and uniform growth of plants as compared with disturbed and irregular growth in unenclosed controls, is demonstrated. These original observations propose a new strategy to suppress or prevent allergic reactions and possibly other effects observed in various human pathologies in relation to a disturbance of human body frequencies. It is hypothesized that the double helix structure of desoxyribonucleic acid (DNA) could be modified by environmental electromagnetic fields and that disresonance between the two chains of DNA could lead to the expression of specific pathology.
To pose a new hypothesis of schizophrenia that affirms and unifies conventional hypotheses.
Outside the brain, there are 5-HTP-containing argyrophil cells that have tryptophan hydroxylase 1 without l-aromatic amino acid decarboxylase. Monoamine oxidase in the liver and lung metabolize 5-HT, rather than 5-HTP, and 5-HTP freely crosses the blood-brain barrier, converting to 5-HT in the brain. Therefore I postulate that hyperfunction of 5-HTP-containing argyrophil cells may be a cause of schizophrenia. I investigate the consistency of this hypothesis with other hypotheses using a deductive method.
Overactive 5-HTP-containing argyrophil cells produce excess amounts of 5-HTP. Abundant 5-HTP increases 5-HT within the brain (linking to the 5-HT hypothesis), and leads to negative feedback of 5-HT synthesis at the rate-limiting step catalysed by tryptophan hydroxylase 2. Owing to this negative feedback, brain tryptophan is further metabolized via the kynurenine pathway. Increased kynurenic acid contributes to deficiencies of glutamate function and dopamine activity, known causes of schizophrenia.
The 5-HTP hypothesis affirms conventional hypotheses, as the metabolic condition caused by acceleration of tryptophan hydroxylase 1 and suppression of tryptophan hydroxylase 2, activates both 5-HT and kynurenic acid. In order to empirically test the theory, it will be useful to monitor serum 5-HTP and match it to different phases of schizophrenia. This hypothesis may signal a new era with schizophrenia treated as a brain-gut interaction.
It is postulated that the immune reaction on chemical carcinogens can inhibit or stimulate the chemical-induced carcinogenesis depending on the individual peculiarities of the synthesis of antibodies. Critical events take place on the barriers between external and internal media. Antibodies to chemical carcinogens, which are secreted into the digestive or bronchial tract, bind the environmental carcinogens and prevent them from penetrating into the blood through the epithelium and thereby inhibit the beginning of the tumour growth in any organs. On the contrary, the serum antibodies promote the penetration of carcinogens through the digestive and bronchial epithelia and thereby stimulate carcinogenesis in the proper organs. The other events take place in the organs such as breast and prostate where carcinogens are transported from the blood. Secretory antibodies bind carcinogens in the blood and transport them through the epithelium of these glands and thereby stimulate the tumour origin in these organs. Antibodies, which are not secreted into the ducts of breast and prostate, hold carcinogens in the blood and thereby inhibit carcinogenesis in these organs. Antibodies to steroid hormones function in the same way, i.e., secretory antibodies stimulate, while the serum antibodies inhibit the genetoxic action of the hormones on breast and prostate. The stimulation of carcinogenesis in the lymphoid cells is realized owing to hapten-specific binding of carcinogens by the membrane receptors of the corresponding clones. Antibodies to the natural inhibitors of carcinogenesis (retinoids, tocopherole, etc.) stimulate the beginning of the tumour growth. Antibodies to carcinogens and antiidiotypic antibodies to the cytochromes p-450 may act as abzymes, i.e., as cytochromes p-450 and thereby increase the level of the carcinogen metabolites.
Antitumour chemotherapy is nowadays a very active field of research, DNA targeting drugs being the most widely used group in therapy. The design, synthesis and anticancer activity of a new class of anticancer derivatives with pyrrolo-1,2-diazine and benzoquinone skeleton is presented. The synthesis is direct and efficient, involving an alkylation followed by a [3+2] dipolar cycloaddition. The penta- and tetra-cyclic pyrrolo-1,2-diazine were evaluated for their in vitro anticancer activity against an NCI 60 human tumour cell line panel. The pentacyclic-1,2-diazine exhibit a significant anticancer activity against Non-Small Cell Lung Cancer NCI-H460, Leukemia MOLT-4, Leukemia CCRF-CEM and Breast Cancer MCF7. We hypothesize that these molecules will exert their anticancer activity through multiple mechanisms of action: intercalating the DNA, inhibiting the topoisomerase enzymes and, destroying the DNA strands via electron transfer mechanism. However, the intercalation with the DNA seems to prevail in competition with the others mechanisms.
A hypothesis is presented according to which the hypocalciuria in preeclamptic women is due to a decreased efficiency of intestinal calcium absorption as a consequence of diminished placental synthesis of 1,25-dihydroxyvitamin D related to lower circulating placental lactogen level and/or a possible reduction in the synthesis of insulin-like growth factor I.
Following solar ultraviolet radiation, epidermal 7-dehydrocholesterol is converted to previtamin D3, which then undergoes a thermal isomerization into vitamin D3. The metabolism of vitamin D3, which is usually considered as an inactive compound, gives rise to the active hormone 1,25-dihydroxyvitamin D3, following two hydroxylation steps occurring in liver and kidney. Here, we propose that this anabolic pathway can also be interpreted as a catabolic one leading to the degradation of the photoproducts of 7-dehydrocholesterol, for which a specific biological role in the skin is proposed.
Aggressive fibromatosis (AF), also known as desmoid tumor is a monoclonal fibroblastic proliferation in a collagen matrix that arises in musculoaponeurotic structures. Though considered as benign, they are locally invasive and their propensity for recurrence after conservative surgery is well documented. Addition of postoperative adjuvant radiotherapy produces higher local control rates, although recurrence rates are still high in patients with positive margins. The antineoplastic activity of vitamin D has been demonstrated both in vitro and in vivo models of several cancers. The proposed mechanisms for antineoplastic activity include inhibition of proliferation associated with cell cycle arrest, induction of apoptosis and reduction in invasiveness and angiogenesis. It has also been shown that vitamin D has a negative impact on collagen homeostasis by inhibiting the formation and increasing its degradation. Since vitamin D has an antineoplastic activity and negative effect on collagen synthesis and deposition, it is proposed that 1,25-dihydroxy vitamin D3 can be a right therapeutic option for the management of desmoid tumors.
In Malignant Hyperthermia an increased open probability of the ryanodine Ca(2+)-channels in the SR-membrane primes a higher cytosolic Ca(2+)-concentration. This in turn accelerates ATP-hydrolysis culminating in a gradual decrease in ATP-levels. At low ATP-levels, IP3-synthesis is being stimulated and the ability of IP3 to release Ca2+ is enhanced. This results through the opening of IP3-dependent channels. Ca(2+)-release through the ryanodine channels and the IP3-dependent channels summate to increase the cytosol Ca(2+)-levels to such a high value that ATP is hydrolysed below a critical value causing rigor (contracture) of skeletal muscle. Since Ca(2+)-uptake by the SR is ATP-dependent, Ca(2+)-uptake will eventually also slow down and so contributes to the rise in cytosol Ca(2+)-concentration.
Reduction of hepatic glucose output has been shown to be the chief basis for metformin's clinical benefit in diabetes, and the balance of the evidence suggests that this reflects inhibition of gluconeogenesis. Recent research with hepatocyte cell cultures demonstrates increased flux through pyruvate kinase in metformin-treated cells. An analysis of the conditions under which clinically relevant concentrations of metformin inhibit gluconeogenesis in hepatocyte cultures prompts the hypothesis that metformin potentiates the allosteric activation of pyruvate kinase by fructose-1,6-diphosphate. This model rationalizes several salient features of metformin's clinical activity: its ability to reduce hepatic triglyceride synthesis, its appetite-suppressant effect, and its failure to induce hypoglycemia.
Extremely low frequencies, from 1 to 1.1 Hz, imprinted in water (imprinting was done by succussing a glass containing the water) led to a total abrogation of a facial seborrhoeic dermatitis, previously proposed as a visible model for the theory of 'memory of water'. This technique provides a new perspective on the enigma of homoeopathy and the treatment of allergic diseases and possibly all other inflammatory reactions.
The Thomson Scientific Impact Factor (IF) for Medical Hypotheses has risen to 1.299 for 2006. This means that the IF has more than doubled since 2004, when it stood at 0.607. Using Elsevier's Scopus database; in 2004 there were 437 citations to Medical Hypotheses papers published in the previous two years--by 2006 this had trebled to 1216 citations. Monthly internet usage of Medical Hypotheses run at an average of about 26000 papers downloaded per month. An IF of 1.3 means that Medical Hypotheses has now entered the mainstream level of 'respectable' medical journals, in terms of its usage by other scientists. This is particularly pleasing given the aim of the journal is to publish radical and speculative ideas. A healthy IF is important to Medical Hypotheses because the journal deploys a system of editorial review, rather than peer review, for evaluation and selection of papers. Editorial review involves selection of a journal's content primarily by an editor who has broad experience and competence in the field, assisted by a relatively small editorial advisory board. The great advantage of editorial review is that it is able, by policy, to favour the publication of revolutionary science. But since editorial review relies on hard-to-quantify and non-transparent individual judgments, it is important for its outcomes to be open to objective evaluations. Scientometric measures of usage such as citations, impact factors and downloads constitute objective evidence concerning a journal's usefulness. Since Medical Hypotheses is performing adequately by such criteria, this provides a powerful answer to those who fetishize peer review and regard any other system of evaluation as suspect. Journal review procedures are merely a means to the end, and the end is a journal that serves a useful function in the dynamic process of science. Medical Hypotheses can now claim to perform such a role.
Twenty years ago the fetal antigen hypothesis was proposed as a potential mechanism by which women are naturally immunized against cancer antigens by antigens from their fetus. Evidence from recent clinical studies shows that a high percentage of parous woman, but not nulliparous women, show evidence of immunization to antigens found on breast, ovarian and endometrial cancer cells. I suggest that this maternal immunization also affects the fetus, causing early immune rejection of fertilized ova that express cancer-related genotypes. Additional cancers, and perhaps even other types of genetic diseases, may be involved in this mechanism.
The possibility that neuropeptides, in particular members of the tachykinin family are involved in inflammatory joint disease is widely disputed. Both clinical and experimental observations indicate that the tachykinin substance P (SP) may be involved in the pathogenesis of arthritis. We have studied the effects of tachykinins and the metabolites of SP on chondrocyte function. We have shown that the C-terminal pentapeptide sequence; H-Phe-Phe-Gly-Leu-Met-NH2 is biologically active in bovine chondrocyte cultures. The production of SP7-11 is limited by hydrolysis of the intact peptide by neutral endopeptidase (E.C. 220.127.116.11). The regulation of this enzyme would modulate the activity of substance P on articular cartilage chondrocytes.
The Publisher regrets that this article is an accidental duplication of an article that has already been published in Medical Hypotheses, doi:10.1016/j.mehy.2007.08.005. The duplicate article has therefore been withdrawn.
Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by the accumulation of mature neoplastic B-lymphocytes. Typically, CLL follows an indolent course, with most patients surviving for many years. However, 10-20% of CLL patients carry 11q23 chromosomal deletions and often exhibit a more severe disease course, with earlier onset of symptoms, shortened lymphocyte doubling time, poor response to therapy, and shortened survival. The molecular basis for 11q23 deletions resulting in a poor prognosis is currently poorly understood. The tumor suppressor gene, ataxia-telangiectasia mutated (ATM, 11q22.3-23.1), is considered a likely candidate gene whose loss could result in the poor prognosis associated with 11q23 deletion and is mutated in a significant percentage of CLL cases. Recently, recombinant ATM expression in ATM-deficient cells was found to decrease transferrin receptor (TfR) expression, suggesting that deletion of the chromosomal region carrying ATM results in increased TfR expression. TfR imports iron into cells, an event necessary for DNA synthesis and cell growth. Additionally, rapidly growing malignant cells, including lymphomas and CLL, often express high TfR levels. Based on this, we propose that one molecular mechanism by which 11q23 deletions confer a poor prognosis in CLL is via increased TfR expression secondary to ATM loss, resulting in the increased cellular iron import, and hence increased capacity for malignant growth. Our hypothesis may also partially explain why gallium, an atomically iron-like toxic metal that binds to transferrin and the TfR is incorporated into cells and was previously demonstrated to have anti-tumor activity in patients with lymphomas refractory to other chemotherapeutic treatments.
The adverse and beneficial effects of postmenopausal hormone replacement therapy include: ischemic heart disease, stroke, pulmonary embolism, breast cancer, an increased rate of onset of asthma as well as reductions in the incidence of diabetes in women with known coronary artery disease and osteoporotic fractures. These varied effects can be explained by the down regulation of 11beta-hydroxysteroid dehydrogenase by estradiol, which results in a reduction of tissue specific cortisol production. The reduction in local cortisol production which diminishes the endogenous anti-inflammatory effects, also allows for the progression of both vascular and pulmonary inflammation. The decrease in cortisol activation reduces insulin resistance and anti-proliferative effects thereby reducing the potential for diabetes but allowing for the emergence of malignancy. Furthermore, the decreased local tissue availability of cortisol reduces the tendency for the development of osteoporosis. New techniques and drugs are being developed to evaluate the modulation of 11beta-HSD1 activity. Further study should result in new ways to control both inflammation and metabolism.