ANOXEMIA AND BRAIN DISEASE

The author advances the concept that anoxemia, either in its general or restricted form, or both, is probably responsible for a considerable portion of “degenerative diseases,” whose etiologic delineation has not yet been traced. It is necessary, he believes, to enlarge greatly the comprehension of the disordered circulatory states to include oxygen want and thereby account for a number of conditions hitherto considered to be of unknown cause. More than this, he finds in oxygen want an explanation of the mechanism of a number of individual lesions or details of lesions otherwise not well understood. The author believes it is very likely that an understanding of cerebral anoxia in its ultimate ramifications will open still wider doors to the understanding of certain clinical syndromes the cause of which remains obscure.     

ANOXIA AND THE CONVULSIVE STATE

The author believes he has clinical and experimental evidence to suggest that one of the underlying causes of idiopathic epilepsy lies in lack of sufficient oxygenation of the cerebrum before or during birth.     

Personality Factors Associated with Frequency of Marijuana Use

A number of personality and style-of-life variables were found to be significantly related to frequency of marijuana use, in a study of 1215 students on the University of California, Los Angeles, campus. Compared with the non-user, in composite the typical marijuana-user is somewhat depressed, more inclined to doubt his emotional adjustment. He likes to take risks and seeks stimulation; he has strong political opinions; he believes in punishment for law-breakers, but he is more likely to question it. He is not religious; he is less well identified with parents, and he has a lower opinion of their marital adjustment. He is not decisive about career goals; he is a fine arts or liberal arts major. He uses alcohol, sometimes in combination with marijuana; he first tried marijuana after entering college and is not increasing his use. The typical marijuana-user in the sample uses it infrequently, twice a month or less often, and is not likely to be using other drugs. The frequent user probably uses other drugs.     

The laboratory rabbit: an animal model of atherosclerosis research

The aim of the present mini review is to describe the laboratory rabbit, an animal that has been widely used for the study of atherosclerosis, the leading cause of mortality in Western society. Due to the fact that the rabbit exhibits hypercholesterolaemia within a few days of an administration of a high cholesterol diet, it is very sensitive to the inducement of atheromatic lesions. The administration of different types of diets can cause different types of lesions. Although these lesions do not develop as tissue plaques, a great number of researchers use this animal model to test the effectiveness of drugs because of their similarity to human fatty streaks. The generation over recent years of transgenic rabbits with alterations in specific genes is expected to help with the elucidation of the mechanisms underlying the initial and developmental stages of the disease. The laboratory rabbit is significantly broadening our understanding on the pathogenesis of atherosclerosis.     

Another Crisis in Psychology

A psychologist in Hungary today does not necessarily want to be acknowledged for what he does as a scientist; actually, the number of those who fancy themselves artists or magicians is growing. On the other hand, those of us who make a point of our theoretical or practical work's being of a scientific nature are willing to consider psychology a natural science. But how could something be scientific if not in the same way physics, chemistry, and biology are?     

THE INSENSITIVITY OF PARAMECIUM TO CYANIDE AND EFFECTS OF IRON ON RESPIRATION

1. The effects of KCN and iron salts on oxygen consumption has been studied in the cell of Paramecium caudatum by manometric methods. 2. KCN solutions of strengths from M/200 to M/10,000 have been shown to produce no decrease in oxygen consumption, but have in most cases produced a very slight increase in the respiration rate. 3. The pH values were found to have little or no effect on these results. 4. Iron salts produce either no effect or a great diminution of oxygen consumption, in no case causing stimulation of rates of respiration. 5. Iron salts in neutral solutions do not penetrate the Paramecium cell nor do they cause so marked an effect as in an acid state. 6. The iron-content of Paramecium was found to be extremely small and not demonstrable by delicate tests. It is believed that iron is not combined in the cell in the form of a respiration-catalyst sensitive to cyanide.     

On Presenting Results of Statistical Analyses in Scientific Journals

In many biological and other scientific journals, a reader's understanding of a paper to the argument of which statistical methods and analyses are important is often impeded by confusions of terminology and ambiguities of symbols. This is not solely because statistics is a difficult subject for biologists! If an editor were to formulate and make known a code of statistical symbols, abbreviations, and technical terms that in his journal will be regarded as part of the normal language of science, an author could use these without need for explanation each time. Every author would remain free to depart from the code, provided that he defined clearly his own usages. Such a policy, supported by the journal's referees, would do much to remove the frequent necessity for a reader to guess an author's meaning. Similarly considerations apply to the use of statistical software packages, where there is an evident need for an author to declare what software (if any) he has used, in much the same way as, by established custom, he will carefully specify his experimental materials and methods where these in any respect differ from the obvious. The present paper is written to stimulate constructive debate, and in no way to dogmatize on the merits or faults of particular statistical methods. Its underlying spirit is that the author of a scientific communication has a duty to describe the making of his observations, the conduct of his computations, and the performance of his computations with a clarity that would permit their repetition by another scientist who has access to the appropriate facilities and resources.     

Some problems of radiation diagnosis of colon cancer

The paper gives the view of the author who is based on his many-year experience in studying a role of radiation diagnosis of colon cancer. It shows it necessary to enhance the significance of radiation diagnosis. More attention should be given to the traditional section on the current radiation study of the large bowel: to irrigoscopy and single double contrasting. By taking into account the labor-consumption of irrigoscopy, the author suggests that the procedure should be simplified without losing its diagnostic capacities. However, he considers single double contrasting of the bowel to be the optimum technique of traditional X-ray study of the bowel in detecting its tumors. Pneumocolonoscopy and iliocecal node study of the ileocecal angle are given in the paper as supplementary techniques of traditional X-ray study of the large bowel. Emphasis is also placed on the role of radiation diagnostic techniques, such as ultrasound diagnosis, X-ray computed tomography, and magnetic resonance imaging. By highly appreciating their significance in the diagnosis of colon cancer, the author believes that they should play a role of important, but additional ways of detecting this pathology. By pointing out the excellent capacities of fibrocolonoscopy, as applied to the problem discussed in the paper, the author does emphasize the certain limitations of this technique, by taking into account that its application can cause some complications. The author's opinion that the obvious increase in the incidence of endophytic carcinomas drastically enhances the role of their radiation diagnosis, but by obligatorily correcting currently available principal methodic and semiotic directives, runs through the entire paper.     

Cytogenetic insights into DNA damage and repair of lesions induced by a monomethylated trivalent arsenical

Arsenic is a human carcinogen, and only recently animal models have been developed that are useful in investigating its carcinogenic mode of action (MOA). However, how arsenic induces cancer is still an open question. In a previous paper, we proposed a model detailing how arsenic might induce DNA lesions leading to cytogenetic damage [A.D. Kligerman, A.H. Tennant, Toxicol. Appl. Pharmacol. 222 (2007) 281–288]. In this model we hypothesized that arsenic does not induce chromosome damage via DNA adduction but induces short-lasting lesions from the action of reactive oxygen species (ROS). These lesions cause single-strand breaks (SSB) that induce chromosome breakage when treatment is in late G₁- or S-phase. However, if treatment is confined to the G₀- or early G₁-phase of the cell cycle, it is predicted that little or no cytogenetic damage will result at the subsequent metaphase. Here, we describe the results from testing this model using monomethylarsonous acid (MMA^III) and cytosine arabinoside (araC), a DNA chain terminator, to extend the time that DNA lesions remain open during repair to allow the lesions to reach S-phase or interact to form DNA exchanges that would lead to exchange aberrations at metaphase. The results of our study only partially confirmed our hypothesis. Instead, the results indicated that the lesions induced by MMA^III are quickly repaired through base excision repair, that there is little chance for araC to extend the life of the lesions, and thus the DNA damage induced by arsenicals that leads to chromosome aberrations is very short lived.     

Severe limitations of the FEve metric of functional evenness and some alternative metrics

The metric of functional evenness FEve is an example of how approaches to conceptualizing and measuring functional variability may go astray. This index has several critical conceptual and practical drawbacks:

1. Different values of the FEve index for the same community can be obtained if the species have unequal species abundances; this result is highly likely if most of the traits are categorical.
2. Very minor differences in even one pairwise distance can result in very different values of FEve.
3. FEve uses only a fraction of the information contained in the matrix of species distances. Counterintuitively, this can cause very similar FEve scores for communities with substantially different patterns of species dispersal in trait space.
4. FEve is a valid metric only if all species have exactly the same abundances. However, the meaning of FEve in such an instance is unclear as the purpose of the metric is to measure the variability of abundances in trait space.

We recommend not using the FEve metric in studies of functional variability. Given the wide usage of FEve index over the last decade, the validity of the conclusions based on those estimates is in question. Instead, we suggest three alternative metrics that combine variability in species distances in trait space with abundance in various ways. More broadly, we recommend that researchers think about which community properties (e.g., trait distances of a focus species to the nearest neighbor or all other species, variability of pairwise interactions between species) they want to measure and pick from among the appropriate metrics.     

Steam engine time: A review of ‘Ending Ageing’ by Aubrey de Grey

Aubrey de Grey has summarised his ideas on Strategies for Engineering Negligible Senescence - SENS - into his book Ending Ageing. He groups the molecular and cellular damage that result from ageing into seven categories, and describes what he believes are approaches to treating or reversing all of them. Some are relatively simple, some very radical, but, even if they are implemented imperfectly, de Grey believes that healthy lifespan would be extended significantly and some adults alive today would live healthily and productively to be 120 or beyond. At that point, further development of anti-ageing technology would extend their life further, and so on. The key is the practicality of technologies for addressing the basis of ageing today. The book is unashamedly a polemic and a plea for support for this grand vision, and its partisanship, first-person conversational style and occasionally immoderate comments may distract some readers from its message. This would be a shame. I think the vision unrealistic in its extreme version, but worth pursuing for its more modest aims, and the book worth reading for its bold ideas and its ability to stimulate the receptive mind to think about how its grand vision might be reduced to practice, to the benefit of us all. Above all, for readers of this Journal, it is an example of how carefully argued hypotheses can make you think and (I hope) act.     

The reversible binding of oxygen to sulfhemoglobin.

The O2 binding properties of sulfhemoglobin were studied. The oxygen tension required for half-saturation of sulfhemoglobin is more than 2 orders of magnitude higher than that for hemoglobin A. The binding of O2 exhibits an alkaline Bohr effect larger than that observed for hemoglobin, yet the Hill number is unity. From the Bohr titration curve, 0.68 proton is released during O2 binding at 0 degrees C. Sulfhemoglobin prepared from carboxypeptidase A-treated hemoglobin has an affinity for O2 which is about the same as that of sulfhemoglobin at the theoretical limit of the Bohr titration curve. Like its carboxypeptidase A-treated hemoglobin precursor, this sulfhemoglobin does not bind O2 cooperatively. Thus, sulfhemoglobin appears to be in a high affinity form at alkaline pH and a low affinity form at acid pH, similar to hemoglobin A. These results demonstrate that the magnitude of the Hill number is not always an indicator of the interaction between oxygen binding and other functions in a hemoglobin.     

Damage pattern as a function of radiation quality and other factors

An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex primary DNA damage and resulting fixed critical cellular lesions translate into linearity for radiation-induced cancer. To solve this enigma, a quantitative assessment of all genotoxic and harmful non-genotoxic agents affecting the human body would be needed.     

THE LARGE INGUINAL RING—Its Significance in the Diagnosis of Inguinal Hernia

A large external inguinal ring is often reported by a medical examiner as a “potential hernia.” This finding may cause the subject to be denied job opportunities and may make him apprehensive about many normal activities.The author believes that unless a sac is present and is causing symptoms that necessitate surgical relief, the term hernia should not be used, regardless of how it is qualified. The ordinary intraabdominal stresses due to coughing, sneezing, etc. increase intraabdominal tension more than heavy lifting, except with loads of nearly the body''s own weight. The lifetime effect of such stresses can contribute to the development of a direct hernia, but most of these cannot be eliminated.     

Mutagenicity and repair of oxidative DNA damage: insights from studies using defined lesions

Oxidative DNA damage has been implicated in mutagenesis, carcinogenesis and aging. Endogenous cellular processes such as aerobic metabolism generate reactive oxygen species (ROS) that interact with DNA to form dozens of DNA lesions. If unrepaired, these lesions can exert a number of deleterious effects including the induction of mutations. In an effort to understand the genetic consequences of cellular oxidative damage, many laboratories have determined the patterns of mutations generated by the interaction of ROS with DNA. Compilation of these mutational spectra has revealed that GC → AT transitions and GC → TA transversions are the most commonly observed mutations resulting from oxidative damage to DNA. Since mutational spectra convey only the end result of a complex cascade of events, which includes formation of multiple adducts, repair processing, and polymerase errors, it is difficult if not impossible to asses the mutational specificity of individual DNA lesions directly from these spectra. This problem is especially complicated in the case of oxidative DNA damage owing to the multiplicity of lesions formed by a single damaging agent. The task of assigning specific features of mutational spectra to individual DNA lesions has been made possible with the advent of a technology to analyze the mutational properties of single defined adducts, in vitro and in vivo. At the same time, parallel progress in the discovery and cloning of repair enzymes has advanced understanding of the biochemical mechanisms by which cells excise DNA damage. This combination of tools has brought our understanding of DNA lesions to a new level of sophistication. In this review, we summarize the known properties of individual oxidative lesions in terms of their structure, mutagenicity and repairability.     

Infecciones hospitalarias aspergilosas bronco-pulmonares en lactantes y niños menores

Routine histological investigations of the lungs of 38 children led to the discovery during the second half of 1970 of 4 cases of pulmonary aspergillosis in hospitalized children between 3 1/2 weeks and 2 years of age. Those cases represented 10.5% of all children, autopsiated during this period with an hospitalization period of more than 7 days. In two cases Aspergillus filaments did not invade pulmonary tissue, but in the two other cases Aspergillus mycelium had invaded the walls of adjacent pulmonary arteries with resultant arteritis, thrombosis and hemorrhagic infarction. The author believes, that the mycoses were acquired by inhalation of contaminated air. But he can not base this supposition of factual evidence.     

CANCER DETECTION—A County Medical Society Program,Riverside, California

Cancer detection examinations by physicians in their private offices were performed as a county medical society project for a period of one year.In a series of 6,765 patients examined, approximately 600 were found to have lesions clinically suspect for tumor. The total number of proven cancers discovered was 280 and the number of lesions classified as precancerous was 87.This percentage of tumors discovered compares favorably with reports from special cancer detection centers formerly utilized in other parts of the country.The Cancer Commission believes that periodic health examinations of persons over the age of 40 in the offices of private physicians is a practical approach to the problem of earlier detection of tumors at accessible sites—the tumors that are the most readily curable by current surgical and radiotherapeutic techniques.     

Mechanisms of free radical-induced damage to DNA

Abstract

Endogenous and exogenous sources cause free radical-induced DNA damage in living organisms by a variety of mechanisms. The highly reactive hydroxyl radical reacts with the heterocyclic DNA bases and the sugar moiety near or at diffusion-controlled rates. Hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to adduct radicals, further reactions of which yield numerous products. These include DNA base and sugar products, single- and double-strand breaks, 8,5′-cyclopurine-2′-deoxynucleosides, tandem lesions, clustered sites and DNA-protein cross-links. Reaction conditions and the presence or absence of oxygen profoundly affect the types and yields of the products. There is mounting evidence for an important role of free radical-induced DNA damage in the etiology of numerous diseases including cancer. Further understanding of mechanisms of free radical-induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importance for disease prevention and treatment.